The Cordillera Central is a vast mountain range, spanning 22,500 km2 in the Philippines, containing some of the country’s last remaining intact forests. These forests are a reservoir for biodiversity and home to many poorly-known species, including those in the genus Rafflesia, renowned for containing the world’s largest flowers. Here we describe Rafflesia balatociana, a distinctive yet overlooked taxon from the high elevation moss forest, which we name after the Balatoc Indigenous Peoples, one of the subtribes in the Kalinga Province. This species is distinguished from its close relatives by a combination of conspicuous and stable characters including a double-dentate disk rim and strap-shaped lacuna on the annulus interior. We compare R. balatociana with co-occurring species in the Cordillera Central, provide a key, and consider our findings in the wider context of the exceptional biodiversity of this region and its conservation requirements. We propose R. balatociana should be classified as Critically Endangered, and recommend its habitat be declared as either a Critical Habitat Area (CHA) or a Local Conservation Area (LCA).

Amphibians are among the most threatened vertebrate taxa globally. Their global decline necessitates effective conservation actions to bolster populations across both the larval and adult life stages. Constructing man-made ponds is one such action proven to enhance reproduction in pond-breeding amphibians. However, to achieve successful conservation outcomes, extensive prior knowledge about the ecology and behaviour of the target species is required. In this study, we investigated how different hydroperiod regimes impact the growth and development of Litoria littlejohni tadpoles. Over a 28-week period, tadpoles were exposed to three hydroperiod treatments: Constant High, Declining, and Constant Low water levels. Weekly measurements of snout-to-vent length, body mass, and Gosner stage were taken to assess any treatment-related changes. To determine whether different treatments affected locomotor performance, a jump test was conducted three weeks post metamorphosis. Individuals did not exhibit developmental plasticity in response to declining water, with a mean time to metamorphosis of 93.3 days. Comparatively, when L. littlejohni tadpoles were exposed to low water volumes, they were able to speed up development and reduce time to metamorphosis, with a mean time of 56.5 days. The speeding up of development had an apparent consequence for L. littlejohni. We found support for trade-offs between rapid development and reduced morphometric measurements post-metamorphosis which resulted in reduced locomotive ability. Individuals from Constant Low water treatments exhibited an average total jumping distance of 170.5 cm over 10 consecutive jumps, compared to 235.8 cm in Constant High and 209.5 cm in Declining treatments. Rapid larval development aids tadpoles in escaping suboptimal aquatic conditions, but its effects on locomotion may impact foraging efficiency and predator escape ability. Understanding developmental plasticity in threatened amphibians, especially in response to hydroperiod variations, is crucial for conservation programs, particularly under future climate change scenarios predicting increased drought and reduced hydroperiods in aquatic environments.

Efficient methane conversion to methanol remains a significant challenge in chemical industry. This study investigates the direct oxidation of methane to methanol under mild conditions, employing a synergy of non-thermal plasma and Cu-MOR (Copper-Mordenite) catalysts. Catalytic tests demonstrate that the Cu-MOR IE-3 catalyst (i.e., prepared by three cycles of ion exchange) exhibits superior catalytic performance (with 51% methanol selectivity and 7.9% methane conversion). Conversely, the Cu-MOR catalysts prepared via wetness impregnation tend to over-oxidize CH 4 to CO and CO 2. Through systematic catalyst characterizations (XRD, TPR, UV-Vis, HRTEM, XPS), we elucidate that ion exchange mainly leads to the formation of zeolite-confined Cu 2+ species, while wetness impregnation predominantly results in CuO particles. Based on the catalytic performance, catalyst characterizations and in-situ FTIR spectra, we conclude that zeolite-confined Cu 2+ species serve as the active sites for plasma-catalytic direct oxidation of methane to methanol.

Background: Bidirectional data pipelines have emerged as a response to the evolving needs of modern data ecosystems. Traditionally, unidirectional pipelines allowed data to flow in a single direction, limiting interaction. The surge in demand for real-time bidirectional communication prompted the development of pipelines that enable two-way data flow, facilitating seamless and dynamic exchanges between source and destination. Objective: The research aims to delve into the role of bidirectional data pipelines within the companies producing and selling software-intensive embedded systems products. Further, the study endeavors to elucidate the fundamental differences between unidirectional and bidirectional data pipelines, shedding light on their unique characteristics. Through comprehensive exploration, it seeks to discern the benefits and challenges inherent in implementing and maintaining bidirectional data pipelines. Furthermore, a critical aspect of the research involves outlining the intricate steps and considerations essential for migrating from unidirectional to bidirectional data pipelines. This includes a focus on prerequisites, methodologies, and the potential benefits derived from such a transition. Method: This study employs a qualitative research approach centered around a multiple-interpretive case study to delve into the complexities of bidirectional data pipelines. Five distinct use cases have been meticulously selected to provide a comprehensive understanding of various aspects of bidirectional data pipelines. Through the in-depth analysis of these concrete use cases, this research aims to elucidate the intricacies, benefits, and challenges associated with bidirectional data pipelines in software-intensive embedded systems environment. Results: The study yielded insightful results on various aspects of bidirectional data pipelines, emphasizing their distinctions from unidirectional data pipelines without a shared data transmission channel. It uncovered the compelling need for bidirectional data pipelines in modern data-centric environments, where the dynamic exchange of information between source and destination is pivotal. The identified benefits ranged from enhanced real-time data synchronization to improved responsiveness in addressing evolving business requirements. Concurrently, the study elucidated inherent challenges, such as increased complexity in pipeline management and potential security considerations. Moreover, the research provided a nuanced understanding of the stepwise process involved in transitioning from unidirectional to bidirectional data pipelines. Conclusion: The study underscores the pivotal role of bidirectional data pipelines in meeting evolving data requirements, offering benefits like real-time synchronization and improved decision-making. Despite their importance, there is a lack of comprehensive research on bidirectional pipelines, prompting the need for further exploration. The transitional journey involves addressing challenges such as data consistency and security concerns while optimizing system design for compatibility. For researchers, the study suggests avenues for optimizing bidirectional pipeline performance, examining long-term impacts, scalability, and real-time anomaly detection. Practitioners can leverage insights for informed decision-making in transitioning to bidirectional data pipelines, aligning organizational needs with their benefits and challenges.

Context: Process Debt, like Technical Debt, can be a source of short-term benefits but often is harmful in the long term for a software organization. Nonetheless, information about Process Debt is scarce in the current literature. Objective: This paper aims to define Process Debt, describe its occurrence with associated risks, and show examples of mitigation strategies. Method: Firstly, we conducted an exploratory study of Process Debt in four international organizations by interviewing 16 practitioners. Then, we validated and extended the findings with a cross-company focus group with additional 10 practitioners. Finally, we analyzed 58 additional observations and 35 interviews from a longitudinal case study. Results: The findings show that Process Debt can be a harmful phenomenon that needs attention. We provide a framework and a definition, and report causes, consequences and occurrence patterns over time of Process Debt. We present mitigation strategies and which ones need further attention for future research. Conclusions: The debt metaphor may help companies understand how to manage and improve their processes and make process-related decisions that are beneficial both in the short and long term.

Intermittent streams exhibit regular patterns of drying and are widespread, but the patterns of drying between geographically close streams are not fully understood. We compared annual patterns of flow and drying among ten intermittent streams within a single drainage basin and determined how traditional hydrologic metrics described variation between streams. We installed stream intermittency sensors and evaluated stage height using low-cost methods. We evaluated landscape factors as potential drivers of flow patterns. Intermittent streams varied based on both high and low flow metrics, driven by a variety of landscape level factors, especially watershed size. Additionally, we compared the observed flow regimes within our system with an established soil and water assessment tool, finding that modeled streamflow patterns generally underrepresented observed drying within the system.

Cancer in the broader sense refers to more than 277 different types of cancer disease. Cancer; is the second leading cause of death, affecting the health of all human societies. Elevated proliferation, angiogenesis, invasion, and metastasis are the hallmarks of cancer. Angiogenesis is a double-edged sword; it is a mechanism that defines the edge between health and disease. Despite its central role in physiological homeostasis, it provides the oxygen and nutrition needed by tumor cells to proceed from dormancy if pro-angiogenic factors tip the balance in favor of tumor angiogenesis. vascular endothelial growth factor (VEGF) is a prominent target among pro-angiogenic factors, in therapeutic methods due to its strategic involvement in the formation of anomalous tumor vasculature. Manipulation in effector molecules like VEGF, PDGF, Integrin αvβ3, FGF, and Eph-B4/ephrin-B2 have played an important role in inhibiting angiogenesis followed by reduced tumor growth and it’s spread. Secondary metabolites such as baicalin, capsaicin, quercetin, EGCG, and lycopene have been found to disrupt angiogenic mechanisms. This work is an attempt to put up a comprehensive approach to understanding the impact of angiogenesis in cancer invasion and their amelioration through phyto-analogs.

Behavioural research over several decades has found that concrete words are processed more quickly and accurately than abstract words (concreteness effect). This advantage is also reflected in their different processing and representation in the human brain. In this electrophysiological study, we explored the interplay of concreteness as a continuous measure and task effects on word processing. Electrophysiological responses of 58 participants were recorded during semantic, affective, and grammatical decision tasks on words parametrically varied in concreteness. Our findings uncovered a fine-grained concreteness effect within four distinct spatiotemporal windows when a coding of semantic information is required. In the semantic decision task, we detected a higher parietal positivity within the P300 time range and an increased left temporo-lateral negative-going amplitude for less concrete concepts. We also identified a concreteness effect characterised by greater negativity in the N400 component. In the affective task, we observed a more pronounced parietal P600-like component for more abstract concepts. Interestingly, we found that the neural representational similarity (starting from 450 ms with a widespread scalp distribution) conformed to the concreteness similarity among concepts (regardless of the task), implying that their semantic representations may be characterised along the concreteness dimension in the brain. Our study transcends the conventional dichotomy of abstract versus concrete words, unearthing not only varied processing dynamics along the concreteness dimension but also distinct fine-grained neural representations. This novel insight positions concreteness as a structural dimension, enriching our comprehension of how the brain organises and processes semantic information.

The evolution of animals and their gut symbionts is a complex phenomenon, obscured by lability and diversity. In social organisms, transmission of symbionts among relatives may yield systems with more stable associations. Here we study the history of a social insect symbiosis involving cephalotine ants and their extracellular gut bacteria, which come predominantly from host-specialized lineages. We perform multi-locus phylogenetics for symbionts from nine bacterial orders, and map prior amplicon sequence data to lineage-assigned symbiont genomes, studying distributions of rigorously defined symbionts across 20 host species. Based on monophyly and additional hypothesis testing, we estimate that these specialized gut bacteria belong to 18 distinct lineages, of which 15 have been successfully isolated and cultured. Several symbiont lineages showed evidence for domestication events that occurred later in cephalotine evolutionary history, and only one lineage was ubiquitously detected in all 20 host species and 48 colonies sampled with amplicon 16S rRNA sequencing. We found evidence for phylogenetically constrained distributions in four symbionts, suggesting historical or genetic impacts on community composition. Two lineages showed evidence for frequent intra-lineage co-infections, highlighting the potential for niche divergence after initial domestication. Nearly all symbionts showed evidence for occasional host switching, but four may, more often, co-diversify with their hosts. Through our further assessment of symbiont localization and genomic functional profiles, we demonstrate distinct niches for symbionts with shared evolutionary histories, prompting further questions on the forces underlying the evolution of hosts and their gut microbiomes.

Epidermolysis Bullosa Pruriginosa Treated with Baricitinib：A Case ReportZhe He1, PhDQian Dong1, PhDYue Xi 1, PhDRui Zheng2, PhD1 Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.Correspondence: Rui Zheng, Email:[email protected]: Epidermolysis Bullosa PruriginosaJAK-STAT: Janus kinase-signal transducer and activator of transcriptionJAK: Janus kinaseDEB: Dystrophic Epidermolysis BullosaVAS: The Visual Analogue ScalAbstract : Introduction: Fewer than 100 cases of Epidermolysis Bullosa Pruriginosa(EBP) have been reported to date. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, and inhibition of this pathway using Janus kinase (JAK) inhibitors might be a useful therapeutic strategy for these diseases. Chronic inflammation is a hallmark of Dystrophic Epidermolysis Bullosa (DEB), thus upregulation of inflammatory cytokines and JAK signaling may play a role in DEB-related pruritus. EBP is a persistent, recurring disease that seriously affects quality of life. Patient concerns: A male patient, 28 years of age, was admitted to our hospital because of recurrent papules, nodules, and intense itching on the trunk and extremities for 12 years. Repeated large and intense itching for 12 years has seriously affected the patient’s normal life.Diagnosis: The patient was diagnosed with Epidermolysis Bullosa Pruriginosa based on examination results. interventions: Oral baricitinib tablets (2 mg, once a day) + Oral desloratadine citrate disodium tablets (8.8 mg, once a day) combined with topical compound flumethasone ointment and Fucidin cream. outcomes: The patient’s skin rashes had subsided and flattened significantly, and his itching was markedly relieved. The Visual Analogue Scal (VAS) itching score of the patient had gradually declined from 8–9 points to 2–3 points. Conclusion : this study confirms that baricitinib is effective and feasible in treating EBP, especially in significantly relieving itching, which rendered new ideas for therapeutic approaches for EBP in the future.Keywords: Epidermolysis Bullosa, kinase inhibitors, Baricitinib Treatment

Molecular ferroelastic with the natural features of mechanical flexibility and switchable spontaneous strain have attracted widespread attention in the scientific community due to their potential applications in tunable gratings, flexible memorizers, strain sensors, and intelligent actuators. However, most designs of molecular ferroelastics remain in the stage of blind exploration, posing a challenge to achieve a functional ferroelastic more effectively. Herein, we have successfully obtained a molecular ferroelastic, [Me2NH(CH2)2NH3](ReO4)2 (Me2NH(CH2)2NH3 = N,N-dimethylethylenediammonium), under the guidance of the mono-/double-protonating strategy. The double-protonated [Me2NH(CH2)2NH3](ReO4)2 undergoes a paraelastic-ferroelastic phase transition with the Aizu notation of 2/mF-1 at 322 K. Meanwhile, the theoretical calculation and experimental measurement simultaneously show that [Me2NH(CH2)2NH3](ReO4)2 possesses good mechanical flexibility, because its elastic modulus (E) of 8.26 GPa and hardness (H) of 0.45 GPa is smaller than the average value of organic crystals (E of 12.05 GPa and H of 0.5 GPa), which makes it promising to apply in wearable pressure sensors, implantable medical sensors, high-precision tuners, etc. This work further enriches the molecular ferroelastic family and demonstrates that mono-/double-protonation is one of the effective molecular modification strategies for designing ferroelastics.

Background & Aims: Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) still exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. The aim of this study was to provide novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Methods: CHB Patients with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. Results: Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with persistently normal ALT (PnALT) levels were matched 1:1 as controls. Ser-Phe-Ala (variable importance in projection [VIP] = 4.28), Lys-Ala-Leu-Glu (VIP = 4.49), 3-methylhippuric acid (VIP = 3.04), 3-methylxanthine (VIP = 2.62), and 7-methylxanthine (VIP = 3.35) were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl-l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Conclusions: Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

IntroductionEpithelioid hemangioendothelioma (EHE) is a rare vascular tumour that originates from vascular endothelial or pre-endothelial cells. Its demographic characteristics are unclear and there is no racial and sex predilection,8The overall incidence of EHE is 0.230 per 1000000 person-years.8 EHE in general affects patients in the age range 16-74 years but EHE of the bone is more prevalent in the third and fourth decade of life.2,3,5EHE can develop in any part of the body but is reported to more frequently in the liver (34%), lungs (21%), bone (19%) and other sites (26%). 1.,2 It was first described and named in 1982 by Weiz and Enzinger and is classified in the 2020 WHO classification of bone tumours as a low-to-intermediate grade neoplasm.2.,3 Malignant vascular bone tumours are rare and constitute less than 1% of primary bone tumours.3 Bone involvement usually involves the lower extremity (62%), upper extremities (14%) and vertebra (10%)3. As such primary EHE of the spine is very uncommon, with the thoracic spine most likely to be involved followed by cervical, lumbar, and sacral levels in order of decreasing frequency3.Here we report on a 26-year-old female with thoracic T2 and T3 lesions in keeping with primary EHE of the spine, her clinical presentation, work up including laboratory, immunohistopathological and imaging studies. We also conclude on her management and current condition. There are currently no prior clinical case reports on primary EHE of the spine in South Africa or Africa as a whole.

Anopheles mosquitos are the primary vectors for the rapid spread of malaria in Limpopo, South Africa, negatively impacting all malaria elimination agenda; particularly for a country with vector control as one of the major malaria elimination strategies. The implementation of vector control strategies, however, depends on the accurate identification of mosquito vectors, which has been lacking in Limpopo as a result of earlier studies that mainly relied on morphological identification of vectors, which has numerous drawbacks that lead to misidentification of mosquitoes, thus resulting in the development and assignment of ineffective control strategies. All this together set back elimination strategies and programs. The present study therefore aimed to molecularly identify mosquitoes collected from various regions within Limpopo province. This was accomplished by examining genetic composition of mosquitos from different regions within Limpopo province, using molecular genetics techniques such as 18S rDNA-based PCR analysis, 18S rDNA sequencing, etc. This investigation was successful since 18S rDNA was able to identify every one of the 42 mosquito samples that were analysed, revealing that the samples belonged to 7 different Anopheles species and the majority of the species were molecularly demonstrated to have been misidentified morphologically. The outcomes of the molecular analysis, which involved comparing the query sequences to the sequences in GenBank, were supported by the close relationship among mosquitoes of the same species in maximum likelihood trees and the presence of high to 100% bootstrap support values, giving confidence to conclude that mosquitoes of the same species under study are genetically related. Due to a number of constraints covered in this study, morphological identification of mosquitoes is prone to misidentification of species, hence genetic characterization is recommended to be used as a confirmatory approach in the identification of the species.

The suitability of ultraviolet (UV) radiation for the decontamination of a surgical face mask was studied by comparing experiments with ray-tracing optical simulations. The 3D fiber network was constructed from X-ray tomography images of the layered mask structure consisting of polypropylene fibers. Both simulations and optical measurements on reflection and transmission indicated that UV light was able to penetrate even the deepest material regions. The decontamination experiments, carried out using Staphylococcus aureus and MS2 microbes, indicated an over 6 log 10 reduction in viable virus contamination of the inner filtering layer. This was achieved within two minutes at a moderate dosage level of 0.22 J/cm 2. The simulations show that despite radiation reflection from the outer mask layer, a significant dosage enters the actual filtering layer due to multiple refraction and scattering of UV light from the inner fibers. This leads to an effective decontamination of fibers with small external UV dosage.

Nucleotide-binding oligomerization domain 2 (NOD2) primarily acts as a cytoplasmic pattern recognition receptor (PRR) recognizing muramyl dipeptide (MDP), the basic unit of bacterial cell wall, playing a key role in the sensing of pathogens. However, accumulating investigations indicate that, in addition to being a PRR, NOD2 also has a wide range of immunomodulatory effects and is involved in the pathogenesis of several inflammatory and infectious diseases, with Crohn’s disease (CD) and leprosy being typical examples. Here, we summarize the MDP dependent and independent activation of NOD2 and the corresponding downstream signaling pathways. In addition to the classic immune response triggered by NOD2, we also review the latest findings of NOD2 regulating immune homeostasis through trained immunity and immune tolerance. Finally, we focus on the diverse roles of NOD2 in defending against mycobacterial infections. A further comprehensive understanding of NOD2 will provide new insights into the treatment of infectious and inflammatory diseases.

Although there have been numerous recent advancements, the prognosis for glioblastoma multiforme (GBM), is still poor. The blood-brain barrier (BBB) places restrictions on GBM treatment. To enhance therapeutic effects, medicines must aggregate at the tumor site. In this review, I discussed RVG29-modified nanoplatforms which were not only able to cross the BBB, but they could accumulate specifically in cerebral glioma tissue. I also discussed the cancer treatment known as magnetic hyperthermia, which involves heating tumor tissues using magnetic nanoparticles under alternating magnetic fields. And I analyzed its use alone and in combination with other adjuvant therapies. Using modified Iron oxide nanoparticles, magnetic hyperthermia can also be used with T1/T2 MRI. Additionally, I examined the use of sonodynamic therapy as a novel and efficient non-invasive way of treating cancer cells. Moreover, I looked over research on photo penetration via the brain’s tissues. In humans’ head (scalp plus skull), the red/NIR (630-810 nm) light penetration ranged from 0.2-10%. In addition, I looked at the superadditive treatment efficacy of using Fe3O4 when combined with photodynamic and photothermal therapy, which demonstrated superior efficacy in eliminating glioma as compared to employing each treatment modality alone or in combination. Finally, according to the superadditive (i.e. “1+1>2”) effect, and the studies we reviewed I believe combining rather safe therapies, such as MHCT, PTT, and PDT with appropriate nanoplatforms that are coated with BBB and GBM cells targeting ligands, Could result in an enhanced GBM therapy and MRI monitoring.

Generalist butterflies are characterized by a broad host repertoire that can comprise several families or even different orders of plants. The genetic and physiological mechanisms underlying the use of such a wide host range are still not fully understood. Earlier studies indicate that the consumption of different host plants is associated with host-specific gene expression profiles. It remained, however, unclear if and how larvae can alter these profiles in the case of a changing host environment. Using the polyphagous comma butterfly (Polygonia c-album) we show that larvae can adjust their transcriptional profiles in response to a new host plant. The switch to some of the host plants, however, resulted in a larger transcriptional response and, thus, seems to be more challenging. At a physiological level, no correspondence for these patterns could be found in larval performance. This suggests that a high transcriptional but also phenotypic flexibility are essential for the use of a broad and diverse host range. We furthermore propose that host switch tests in the laboratory followed by transcriptomic investigations can be a valuable tool to examine not only plasticity in host use but also subtle and/or transient trade-offs in the evolution of host plant repertoires. key words: insect-plant association, host plant adaptation, gene expression, phenotypic plasticity