As an important part of the construction industry, rural residential buildings are characterized by low energy utilization, unreasonable structures and low consumption levels, and it is particularly important to study their low-carbon transformation and evaluation system. In view of the many low-carbon transformation needs of rural residential buildings, the existing research results were analyzed in depth, and the coefficient of variation method was used to identify the important factors affecting the low-carbon transformation of rural residential buildings, and the evaluation system of rural residential buildings’ low-carbon transformation was determined by Analytic Hierarchy Process (APH), and the system was used in a rural residential building low-carbon evaluation study. The results show that the influence of “energy use”, “envelope structure” and “economic factors” on the decarbonization of buildings is obvious, with the weights of 36.4%, 24.5% and 19.5% respectively. Among the secondary indicators, “clean energy utilization”, “electricity consumption”, “external wall insulation system” and “window performance” are the most important factors in reducing carbon emissions in rural areas. The most critical influencing factors for the low carbonization level of clean energy in rural residential buildings are “window performance”. Finally, based on the constructed low carbonization evaluation system, we propose a targeted solution strategy to provide a theoretical basis for the establishment of an effective low carbonization evaluation system for clean energy in rural residential buildings.

Radiotherapy is a mainstay treatment for malignant tumors in clinical. However, enhancing radiation damage to tumor cells meanwhile sparing normal tissues is still a great challenge in radiotherapy. Nanomaterials with high atomic number (Z) values are promising radiosensitizers by promoting the radiation energy deposition in irradiated tumor cells, thus enhancing the therapeutic ratio of radiotherapy. In this review, we described the mechanisms of high-Z element radiosensitizers and systematically summarized the recent progress on metal-based nanomaterials, including high-Z metal nanoparticles, metal-organic frameworks (MOFs) and other high-Z-containing nanomaterials. Finally, further potential and challenges in this field were discussed.

Aims: Older adults are vulnerable to medication-related harm mainly due to high use of medications and inappropriate prescribing. This study aimed to investigate the associations between inappropriate prescribing and number of medications identified at discharge from geriatric rehabilitation with subsequent post-discharge health outcomes. Method: REStORing health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort study of geriatric rehabilitation inpatients. Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were measured at acute admission, and at admission and discharge from geriatric rehabilitation, using version 2 of the STOPP/START criteria. Results: 1890 patients (mean age 82.6 ± 8.1 years, 56.3 % females) were included. The use of at least 1 PIMs, or PPOs at geriatric rehabilitation discharge were not associated with 30-day and 90-day readmission and 3-month and 12-month mortality. Central nervous system (CNS)/psychotropics and fall risk PIMs were significantly associated with 30-day hospital readmission (adjusted odds ratio (AOR) 1.53; 95%CI 1.09─2.15), and cardiovascular PPOs with 12-month mortality (AOR 1.34; 95%CI 1.00─1.78). Increased number of discharge medications was significantly associated with 30-day (AOR 1.03; 95%CI 1.00─1.07) and 90-day (AOR 1.06; 95%CI 1.03─1.09) hospital readmissions. The use and number of PPOs (including vaccine omissions) were associated with reduced independence in instrumental activities of daily living scores at 90-days post geriatric rehabilitation discharge. Conclusion: The number of discharge medications, CNS/psychotropics and fall risk PIMs were significantly associated with readmission, and cardiovascular PPOs with mortality. Interventions are needed to improve appropriate prescribing in geriatric rehabilitation patients to prevent hospital readmission and mortality.

TITLE PAGETitle: Comment on: evaluating age and sex-specific rates of gall bladder disease in children with sickle cell diseaseArticle type: Letter to the editorCorrespondence : 1. Ifra Eeman Ahmed contact : 03335890003 Email : [email protected] : Federal medical & dental college,IslamabadAddress: House#2,Street#15g,Sector A,Bahria Enclave,IslamabadCo-author : 2. Satesh KumarContact: +92-3325252902 Email:Institute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa citi Garden east, KarachiWord count: 391Conflict of interest : NoneDeclaration : NoneAcknowledgment : None

Daratumumab induced Minimal Residual Disease Negative Remission in CD 38 (dim) Positive Pediatric Acute Myeloid LeukemiaPronamee Borah1, Dinah Ng1, Nitin Dayal2, Sangeeta Pathak3, Rahul Naithani11Hematology and Bone Marrow Transplant Division, Max Superspecialty Hospital, Delhi, India2Department of Lab Medicine, Max Superspecialty Hospital, Delhi, India3Department of Transfusion medicine, Max Superspecialty Hospital, Delhi, IndiaConflicts of interest: None to declare.No financial support was obtained in this study.Text word count 815Brief running title: Daratumumab in Pediatric AMLKey Words: Daratumumab, AML, ChildrenTables: 0; Figures: 0

Organic luminogens with persistent room temperature phosphorescence (RTP) have drawn tremendous attentions due to their prom-ising potentials in optoelectronic devices, information storage, biological imaging, and anti-counterfeiting. In this work, six triazatrux-ene-based lumiogens with different peripheral substituents and configurations are synthesized and systematically studied. The results show that their fluorescence quantum yields in solid states range from 15.73% to 37.58%. Dispersing the luminogens as guest into the host (PPh3) could turn on the persistent RTP, where PPh3 acts as not only a rigid matrix to suppress the non-radiative transitions of the guest, but also provides energy transfer channels to the guest. The maximum phosphorescence efficiency and the longest lifetime could reach 29.35% and 0.99 s in co-crystal films of 6-TAT-CN/PPh3 and 5-TAT-H/PPh3, respectively. Moreover, these host-guest co-crystalline films exhibit great potentials in advanced dynamic data encryption and anti-counterfeiting. This work deepens the insight for low cost, halogen-free, and facile fabrication of all-organic persistent RTP materials.

A methodology is proposed to aid parameter estimation in fundamental models of pharmaceutical processes. This methodology addresses situations with insufficient data to reliably estimate all parameters, when the estimation is complicated by uncertain independent variables. The proposed method uses an augmented sensitivity matrix to rank the combined set of parameters and uncertain inputs from most estimable to least estimable. An updated mean-squared-error criterion is then used to determine the appropriate parameters and inputs that should be estimated, based on the ranked list. A model for one step in a batch pharmaceutical production process with an uncertain initial reactant concentration is used to illustrate the method, revealing that the initial reactant concentration in each batch should be estimated along with three out of six model parameters. Non-estimable parameters are fixed at their initial values to prevent overfitting. The method will aid error-in-variables parameter estimation in many situations involving limited data.

New-onset pemphigus after COVID-19Yihang Xie1 Mei Yang1 Peimei Zhou1* Jiaming Fan1 Sijie Zhou11.Department of Dermatovenereology, Chengdu Second People’s Hospital, Chengdu, China* Corresponding Author: [email protected] head: pemphigus after COVID‐19The category of the article: LetterKeywords: COVID‐19, pemphigusManuscript word count: 690 wordsThe number of figures: 2The number of tables: 0The number of references: 8Correspondence to: Peimei Zhou, M.D, Ph.D., Department of Dermatovenereology, Chengdu Second People’s Hospital, Qingyun Street, Chengdu, 610041, China.Tel: +86 18908176315; E-mail:[email protected] conflict of interest statement: Y. Xie, and my co-authors have no conflict of interest to declare.Ethics statement: The patient has consented to publish this information.Data availability statement: Data sharing does not apply to this article as no new data were created or analyzed in this study.Funding sources: noneDear Editor,Cutaneous manifestations of coronavirus disease (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; family Coronaviridae, genus Betacoronavirus, subgenusSarbecovirus ), have been increasingly reported. SARS-CoV-2 infection is multisystemic and leads to potentially detrimental effects on various organs. Maculopapular, urticarial, vesicular, livedoid, and Chilblain-like lesions (CBLL) have been commonly reported to be associated with COVID-191. Here, we encountered an intriguing case of pemphigus that developed after COVID-19 infection.A 73-year-old male presented with a 42-day history of pruritic flaccid blisters that arose on the trunk and both upper limbs on normal and erythematous skin. Cutaneous lesions started 3 days after the positive reverse transcription polymerase chain reaction (RT-PCR) test diagnostic for SARS-CoV-2. He denied any history of systemic diseases, medication, and medicine or food allergies, and had not used any medication before symptom onset. The patient had first been diagnosed with allergic dermatitis caused by COVID-19 at another hospital and was prescribed oral prednisone (8 mg once daily for 4 days). The patient reported no new blisters, but the erythema did not fade; therefore, he visited our hospital. Physical examination revealed cutaneous lesions on the trunk and both upper limbs without mucosal involvement and scattered superficial blisters that developed into crusted erosions on an erythematous base(Figure1 A-D). Laboratory examination revealed normal white cell count (8.63 Ö109/L; normal 3.5-9.5 Ö109/L) with eosinophilia (6%; normal 0.5%-5.0%). Desmoglein (Dsg) 1 antibody levels were > 150 U/mL (positive: > 20), while Dsg3, BP(bullous pemphigoid)180, and BP230 antibody levels were within normal ranges. Other laboratory tests including RT-PCR targeting SARS-CoV-2, immunoglobulin, erythrocyte sedimentation rate, the spectrum of antinuclear antibodies, and T-spot were negative or normal. Chest and abdominal computed tomography revealed chronic inflammatory changes but no obvious tumors. Histological analysis of an incisional cutaneous biopsy taken from the patient’s abdomen showed subcorneal blister formation, acantholytic cells within the blister, and marked spongiotic edema in the spongiosa layer that had mixed inflammatory infiltrate with eosinophils, leukomonocytes, and neutrophils(Figure2A). Direct immunofluorescence (DIF) showed deposition of intracellular IgG and C3 in subepidermal 2/3 interspinous cells, though was negative for IgA and IgM, confirming pemphigus(Figure2B,C). Considering the good response to hormone treatment, the patient continued oral prednisone at 8 mg once daily along with the use of topical corticosteroids. Symptoms were completely absent after 3 weeks(Figure1 E-F).An increasing number of studies on cutaneous manifestations of COVID-19 have been reported; however, knowledge is still lacking on the common skin manifestations of this disease. Nonspecific cutaneous manifestations due to SARS-CoV-2 infection have also been reported, such as immune thrombocytopenic purpura (ITP), dengue-like exanthem, pityriasis rosea-like eruptions, acral ischemia, mucositis, dusky lesions, and bullae2.3.4. We searched all relevant articles and found only two cases of pemphigus vulgaris induced by COVID-19. In the case presented here, we realized that COVID-19 may be responsible for the rash eruption, possibly due to an inflammatory reaction5. The onset time of the rash was similar to that in the cases of pemphigus previously reported by De Medeiros5 and Mohaghegh F6 (within 1.5 months). In our case, although direct immunofluorescence showed subepidermal 2/3 deposition, we still diagnosed pemphigus foliaceus in combination with the pathological presentation, indirect immunofluorescence, and good treatment outcome. We speculate that the reason why direct immunofluorescence showed subepidermal 2/3 deposition may be the marked sponge edema of the epidermis, which may lead to a discontinuity of acantholysis, resulting in leakage of Dsg1 into the deeper epidermis.Pemphigus is defined as a group of rare mucocutaneous autoimmune diseases. Its etiology is unknown, though there are studies on autoimmune etiology which is believed to be related to stimulation by certain drugs, ultraviolet radiation, and malignant tumors; these induce autoimmune reactions by making the adhesive substances between the spiny cell layers become autoantigens7. It is rarely considered, however, that viral infections might cause pemphigus. The ability of SARS-CoV-2 to induce a hyper-stimulated immune state was discovered at the beginning of the pandemic8. As an instrumental trigger of autoimmunity, SARS-CoV-2 infection could be a trigger for autoimmune reactions, possibly through more than one mechanism. Because of this, all factors should be considered in any patient presenting with new-onset or exacerbating cutaneous reactions.

Over three years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variants. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation. Thus, the acquired immunity established among humans is complicated, and there is a lack of understanding within a panoramic vision. Here, we provide the special characteristics of the cellular and humoral responses in 2-year convalescents after inactivated vaccines, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and NAb, but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, inoculation with inactivated vaccine fueled the NAb to BA.1, BA.2, BA.4, and BA.5 in 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed in 2-year convalescents after inoculation. The study provides insight into the complicated features of human acquired immunity to SARS-CoV-2 and variants in the real world, indicating that promoting vaccine inoculation is essential for achieving herd immunity against emerging variants, especially in convalescents.

Some of the most vexing problems of deep level relationship that remain in angiosperms involve the superrosids. The superrosid clade contains a quarter of all angiosperm species, with 18 orders in three subclades (Vitales, Saxifragales and core rosids) exhibiting remarkable morphological and ecological diversity. To help resolve deep-level relationships, we constructed a high-quality chromosome-level genome assembly for Tiarella polyphylla (Saxifragaceae) thus providing broader genomic representation of Saxifragales. Whole genome microsynteny analysis of superrosids showed that Saxifragales shared more synteny clusters with core rosids than Vitales, further supporting Saxifragales as more closely related with core rosids. To resolve the ordinal phylogeny of superrosids, we screened 122 single copy nuclear genes from genomes of 36 species, representing all 18 superrosid orders. Vitales were recovered as sister to all other superrosids (Saxifragales + core rosids). Our data suggest dramatic differences in relationships compared to earlier studies within core rosids. Fabids should be restricted to the nitrogen-fixing clade, while Picramniales, the Celastrales-Malpighiales (CM) clade, Huerteales, Oxalidales, Sapindales, Malvales and Brassicales formed an “expanded” malvid clade. The Celastrales-Oxalidales-Malpighiales (COM) clade (sensu APG IV) was not monophyletic. Crossosomatales, Geraniales, Myrtales and Zygophyllales did not belong to either of our well-supported malvids or fabids. There is strong discordance between nuclear and plastid phylogenetic hypotheses for superrosid relationships; we show that this is best explained by a combination of incomplete lineage sorting and ancient reticulation.

Morphological identification of cnidarian species can be difficult throughout all life stages due to the lack of distinct morphological characters. Moreover, in some cnidarian taxa genetic markers are not fully informative, and in these cases combinations of different markers or additional morphological verifications may be required. Proteomic fingerprinting based on MALDI-TOF mass spectra was previously shown to provide reliable species identification in different metazoans including some cnidarian taxa. For the first time, we tested the method across four cnidarian classes (Staurozoa, Scyphozoa, Anthozoa, Hydrozoa) and included different scyphozoan life-history stages (polyp, ephyra, medusa) into our dataset. Our results revealed reliable species identification based on MALDI-TOF mass spectra across all taxa with species-specific clusters for all 23 analyzed species. In addition, proteomic fingerprinting was successful for distinguishing developmental stages, still by retaining a species specific signal. Furthermore, we identified the impact of different salinities in different regions (North Sea and Baltic Sea) on proteomic fingerprints to be negligible. In conclusion, the effects of environmental factors and developmental stages on proteomic fingerprints seem to be low in cnidarians. This would allow using reference libraries built up entirely of adult or cultured cnidarian specimens for the identification of their juvenile stages or specimens from different geographic regions in future biodiversity assessment studies.

RATIONALE: Sample preparation is one of the most crucial steps for MALDI mass spectrometry imaging (MALDI-MSI). The scientists beginning their adventure with this technique may be overwhelmed by the variety of matrices, solvents, concentrations, the ways of their applications, and the lack of widely available knowledge about the influence of these parameters on the results. Here we would like to present our experiences with detailed aspects of matrices deposition, hopefully helpful for the scientific community. METHODS: In our article, we have tested several MALDI matrices applied by the SunCollect® system: wet-interface matrix deposition in the context of lipids analysis. Among them: 2,5-dihydroxybenzoic acid (DHB), norharmane, N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC), 9-aminoacridine (9AA). We have optimized the number of matrix layers and nozzle settings in terms of spectra intensity and the overall quality of obtained ion maps. RESULTS: Our research presents the influence of the number of matrix layers and nozzle settings on the results and allows for choosing the optimal parameters for the analyses. In positive ionization mode, DHB matrix could be chosen as the first selection. In the negative ionization mode, DAN matrix produces higher peak intensity in a lower mass range and seems to provide more information than 9AA. We recommended NEDC for particular tasks such as glucose analysis. Comparably to remaining matrices, norharmane significantly changes received ion maps. CONCLUSIONS: Dealing with such a great amount of data allows us to notice an interesting conclusion: the obtained ion picture for a particular ion could differ dramatically with changing the matrix, the solvent composition, or even the number of matrix layers. This must be considered when interpreting the result and forces us to compare the results obtained with different matrices with extreme caution.

Rational: Organisms that grow a hard carbonate shell or skeleton, such as foraminifera, corals or molluscs, incorporate trace elements into their shell during growth that absorbs the environmental change and biological activity they experienced. These geochemical signals locked within the carbonate are archives used in proxy reconstructions to study past environments and climates, to decipher taxonomy of cryptic species and to resolve evolutionary responses to climatic changes. Methods: Here we use a laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a time resolved acquisition to quantify the elemental composition of carbonate shells. We present the LABLASTER (Laser Ablation BLASt Through Endpoint in R) package, which imports a single time resolved LA-ICP-MS analysis, then detects when the laser has ablated through the carbonate as a function of change in signal over time, and outputs key summary statistics. We provide two worked examples within the package: a planktic foraminifera and a tropical coral. Results: We present the first R package that improves signal: noise ratios in data reduction workflows by automating the detection of when the laser has ablated through a sample using a smoothed time-series and subsequent removal of off-target data points. The functions are flexible and adjust dynamically to enhance the signal: noise ratio of the desired geochemical target. Visualisation tools for manual validation are also included. Conclusions: LABLASTER increases transparency and repeatability by algorithmically identifying when the laser has either ablated fully through a sample or across a mineral boundary and is thus no longer documenting a geochemical signal associated with the desired sample. LABLASTER’s focus on better data targeting means more accurate extraction of biological and geochemical signals.

Isochromanone is the core structure of many bioactive compounds. Direct oxidation of isochromans is one of leading methods for the construction of isochromanones, while most established processes remain suffering from the use of environmental unfriendly metal oxidants, harsh reaction conditions, and the difficulty in catalyst recycling and production separation. Herein, we report a convenient, cost-effective, and green method for the synthesis of high-value added isochromanones via isochroman oxidations with O2 by a novel heterogeneous vanadium cluster catalyst (Cat.1) under mild conditions. This reaction protocol demonstrates high catalytic activity with good catalyst recyclability and reusability for a wide scope of substrates.

Listening effort can be defined as a measure of cognitive resources used by listeners to perform a listening task. Several methods have been proposed to assess listening effort, but the reliability of these methods has not yet been thoroughly established, which is necessary before using them in research or clinical settings. This study included 32 participants who performed speech-in-noise tasks in two sessions (separated approx. 1 week apart) by listening to Sentences and Word lists presented at different signal-to-noise ratios (-9, -6, -3, and 0 dB). We assessed the test-retest reliability of the self-reported measure of listening effort and frontal midline theta (Fmθ) power, which has been proposed as a neural correlate of listening effort. The reliability of the percentage of correct words was also examined. Relative and absolute reliability was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman analysis, respectively. The standard error of measurement (SEM) and the smallest detectable change (SDC) were also assessed. Overall, the reliability analysis revealed an acceptable between-session variability for the correct words and effort rating. However, Fmθ power showed high variability, which brings into question its use as a reliable correlate of listening effort.

Auditory processing and the complexity of neural activity can both indicate residual conscious-ness levels and differentiate between states of arousal. However, how measures of neural signal diversity, or complexity, manifest in evoked activity, and, more generally, how the electrophys-iological characteristics of auditory responses change in states of reduced consciousness, re-main under-explored. Here, we tested the hypothesis that measures of neural complexity and the spectral slope would discriminate stages of sleep not only in spontaneous EEG, but also in auditory-evoked responses. High-density EEG was recorded in 21 participants to determine the spatial relationship between these measures, and between spontaneous and auditory-evoked signals. Results showed that the complexity and the spectral slope in the 2-20 Hz range dis-criminated between sleep stages and had a high correlation in sleep. In wakefulness, complexity was strongly correlated to the 20-40 Hz spectral slope. Auditory stimulation resulted in reduced complexity in sleep compared to spontaneous activity and modulated the spectral slope in wake-fulness. These findings demonstrate the persistence of electrophysiological markers of arousal during both spontaneous and evoked EEG activity and have direct applications to studies using auditory stimulation to probe neural functions in states of reduced consciousness.

Small-scale horizontal axis wind-turbines (SHAWTs) are acquiring relevance within the regulatory policies of the wind sector aiming at net-zero-emissions, while reducing visual and environmental impact by means of distributed grids. SHAWTs operate transitionally, at Reynolds numbers that fall between 10^5 < Re < 5·10^5. Furthermore, environmental turbulence and roughness affect the energetic outcome of the turbines. In this study, the combined effect of turbulence and roughness is analysed via wind tunnel experiments upon a transitionally-operating NACA0021 airfoil. The combined effects cause a negative synergy, inducing higher drops in lift and efficiency values than when considering the perturbing agents individually. Besides, such losses are Reynolds-dependent, with higher numbers increasing the difference between clean and real configurations, reaching efficiency decrements above 60% in the worst-case scenario. Thus, these experimental measurements are employed for obtaining the power curves and estimating the annual energy production (AEP) of a 7.8 kW-rated SHAWT design by means of a BEM code. The simulations show a worst-case scenario in which the AEP reduces above 70% when compared to the baseline configuration, with such a loss getting attenuated when a pitch-regulated control is assumed. These results highlight the relevance of performing tests that consider the joint effect of turbulence and roughness.

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