Miracle-dz/UniFAR-FTUs huggingface dataset:
Seroprevalence of Hepatitis B, Hepatitis C, Human Immunodeficiency Virus, syphilis, and malaria among blood donors at tertiary care hospital blood bank.

OBJECTIVE To ascertain the frequency of markers of transfusion-transmitted infections among blood donors in a tertiary care setting. METHODS The retrospective cross-sectional descriptive study, was conducted in the Blood Bank section of the Department of Pathology at the Dow University of Health Sciences, Karachi, and comprised data of blood donors from January 2013, to October 2018. All blood donors had been screened for hepatitis B, hepatitis C, human immunodeficiency virus I and II, syphilis through electrochemiluminescence and malaria using immunochromatography. Data was analyzed using SPSS 21. RESULTS Of the 29,732 donors, 29,712(99.93%) were males and 20(0.06%) were females; 12(0.04%) were volunteers and 29,720(99.95%) were exchange donors. Overall, 2587(8.7%) donors were positive for an infectious disease; 908(3%) hepatitis C virus, 887(2.9%) hepatitis B, 620(2%) syphilis, 168(0.5%) human immunodeficiency virus and 4(0.02%) malaria. CONCLUSIONS Hepatitis C and B were the most frequent infections, followed by syphilis in the sample.
COVID‐19 disease trajectories among nursing home residents

Older adults are at greater risk of both infection with and mortality from COVID‐19. Many U.S. nursing homes have been devastated by the COVID‐19 pandemic, yet little has been described regarding the typical disease course in this population. The objective of this study is to describe and identify patterns in the disease course of nursing home residents infected with COVID‐19.
Formulation and quality evaluation of finger millet (Eleusine coracana (L.) gaertn.) flour incorporated biscuits

Replacing the ingredients used in biscuits with potential nutritive ingredients would be beneficial to improve the nutritional quality of the biscuits. Although, finger millet is highly nutritious when compared to other most commonly consumed cereals, limited availability of processed food products in ready-to-eat form has restricted the finger millet consumption. The present study was focused on formulating biscuits by replacing refined wheat flour with finger millet flour. Four biscuit samples were formulated by replacing different percentages of refined wheat flour with finger millet flour. Physicochemical and microbiological properties of the biscuits were evaluated. Nutritional and antioxidant properties of the biscuit, which was formulated by replacing 50% of refined wheat flour with finger millet flour, were evaluated and compared with a control biscuit which was prepared using refined wheat flour. The finger millet flour incorporated biscuit was nutritionally superior to the control biscuit in terms of dietary fibers and polyphenolic compounds including flavonoids. Besides, replacement of refined wheat flour with finger millet flour in biscuit formulation enhanced the antioxidant properties of the biscuit. Therefore, the finger millet flour incorporated biscuit can be considered as a good source of antioxidants.
CMTM4 regulates epithelial–mesenchymal transition and PD‐L1 expression in head and neck squamous cell carcinoma

The epithelial–mesenchymal transition (EMT) is a pivotal step involved in cancer recurrence and metastasis. In addition, the activation of the EMT program can induce a cancer stem cell (CSC)‐like phenotype and programmed death‐ligand 1 (PD‐L1) expression in head and neck squamous cell carcinoma (HNSCC). The CMTM family has reported as an important regulator in this process. Here, we investigated the role of CMTM4 in HNSCC. We indicated that CMTM4 was overexpressed in human and mouse HNSCC samples and in HNSCC cell lines by immunohistochemistry and Western blot. A high expression level of CMTM4 was correlated with advanced lymph node metastasis and a negative prognosis. CMTM4‐knockdown by small interfering RNA downregulated the EMT process and inhibited the migration and invasion abilities of tumor cells. Moreover, knockdown of CMTM4 decreased CSC‐associated markers via the protein kinase B pathway. Notably, CMTM4‐knockdown inhibited the expression of interferon‐γ induced PD‐L1 in HNSCC cells. A positive correlation was found between CMTM4 expression and CD8+ and PD‐1+ cell density in the stroma. Our findings indicated that CMTM4 may play an important role in regulating EMT/CSC phenotypes and PD‐L1 expression. This study may reinforce the interest in CMTM4 as a potential target for the prognosis and treatment of HNSCC.
Good Quality Care for Cancer Patients Dying in Hospitals, but Information Needs Unmet: Bereaved Relatives’ Survey within Seven Countries

Abstract Background Recognized disparities in quality of end‐of‐life care exist. Our aim was to assess the quality of care for patients dying from cancer, as perceived by bereaved relatives, within hospitals in seven European and South American countries. Materials and Methods A postbereavement survey was conducted by post, interview, or via tablet in Argentina, Brazil, Uruguay, U.K., Germany, Norway, and Poland. Next of kin to cancer patients were asked to complete the international version of the Care Of the Dying Evaluation (i‐CODE) questionnaire 6–8 weeks postbereavement. Primary outcomes were (a) how frequently the deceased patient was treated with dignity and respect, and (b) how well the family member was supported in the patient's last days of life. Results Of 1,683 potential participants, 914 i‐CODE questionnaires were completed (response rate, 54%). Approximately 94% reported the doctors treated their family member with dignity and respect “always” or “most of the time”; similar responses were given about nursing staff (94%). Additionally, 89% of participants reported they were adequately supported; this was more likely if the patient died on a specialist palliative care unit (odds ratio, 6.3; 95% confidence interval, 2.3–17.8). Although 87% of participants were told their relative was likely to die, only 63% were informed about what to expect during the dying phase. Conclusion This is the first study assessing quality of care for dying cancer patients from the bereaved relatives’ perspective across several countries on two continents. Our findings suggest many elements of good care were practiced but improvement in communication with relatives of imminently dying patients is needed. (ClinicalTrials.gov Identifier: NCT03566732). Implications for Practice Previous studies have shown that bereaved relatives’ views represent a valid way to assess care for dying patients in the last days of their life. The Care Of the Dying Evaluation questionnaire is a suitable tool for quality improvement work to help determine areas where care is perceived well and areas where care is perceived as lacking. Health care professionals need to sustain high quality communication into the last phase of the cancer trajectory. In particular, discussions about what to expect when someone is dying and the provision of hydration in the last days of life represent key areas for improvement.
StenoSCORE: Predicting Stenotrophomonas maltophilia Bloodstream Infections in the Hematologic Malignancy Population

Stenotrophomonas maltophilia bloodstream infections (BSI) are associated with considerable mortality in the hematologic malignancy population. Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice; however, it is not routinely included in empirical treatment regimens, both because of its adverse event profile and the relative rarity of S. maltophilia infections. ABSTRACT Stenotrophomonas maltophilia bloodstream infections (BSI) are associated with considerable mortality in the hematologic malignancy population. Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice; however, it is not routinely included in empirical treatment regimens, both because of its adverse event profile and the relative rarity of S. maltophilia infections. We developed a risk score to predict hematologic malignancy patients at increased risk for S. maltophilia BSI to guide early (TMP-SMX) therapy. Patients ≥12 years of age admitted to five hospitals between July 2016 and December 2019 were included. Two separate risk scores were developed, (i) a “knowledge-driven” risk score based upon previously identified risk factors in the literature in addition to variables identified by regression analysis using the current cohort, and (ii) a risk score based upon automatic variable selection. For both scores, discrimination (receiver operator characteristic [ROC] curves and C statistics) and calibration (Hosmer-Lemeshow goodness-of-fit test and graphical calibration plots) were assessed. Internal validation was assessed using leave-one-out cross-validation. In total, 337 unique patients were included; 21 (6.2%) had S. maltophilia BSI. The knowledge-driven risk score (acute leukemia, absolute neutrophil count category, mucositis, central line, and ≥3 days of carbapenem therapy) had superior performance (C statistic = 0.75; 0.71 after cross-validation) compared to that of the risk score utilizing automatic variable selection (C statistic = 0.63; 0.38 after cross-validation). A user-friendly risk score incorporating five variables easily accessible to clinicians performed moderately well to predict hematologic malignancy patients at increased risk for S. maltophilia BSI. External validation using a larger cohort is necessary to create a refined risk score before broad clinical application.
Medicinal cannabis use in palliative care.

BACKGROUND Legislative change in recent years allows the prescription of medicinal cannabis for patients receiving palliative care. There appears to be widespread community support of its use in this context. OBJECTIVE The aim of this article is to provide an overview of current research on the use of medicinal cannabis within the palliative care context for both children and adults. DISCUSSION The evidence needed to support the use of medicinal cannabis for symptom control is limited and still emerging. It is unlikely that medicinal cannabis will be used as a first-line agent for the management of pain, nausea and other specific symptoms, but it may have an adjuvant or complementary role in symptom management within palliative care. Consistent with the Therapeutic Goods Administration advice, these authors recommend that general practitioners encourage patients to participate in trials or programs that objectively monitor benefit and toxicity of medicinal cannabis.
Genotype–phenotype correlation in French patients with myelin protein zero gene‐related inherited neuropathy

Preparations for clinical trials of unfolded protein response (UPR) inhibitors (such as Sephin1) that target the upregulated UPR in patients with Charcot–Marie–Tooth disease (CMT) carrying MPZ mutations are currently underway. The inclusion criteria for these trials are still being formulated. Our objective was to characterize the relation between genotypes and phenotypes in patients with CMT caused by MPZ mutations, and to refine the inclusion criteria for future trials.
Genome Scale Analysis Reveals IscR Directly and Indirectly Regulates Virulence Factor Genes in Pathogenic Yersinia

How bacteria adapt to the changing environment within the host is critical for their ability to survive and cause disease. For example, the mammalian host severely restricts iron availability to limit bacterial growth, referred to as nutritional immunity. ABSTRACT The iron-sulfur cluster coordinating transcription factor IscR is important for the virulence of Yersinia pseudotuberculosis and a number of other bacterial pathogens. However, the IscR regulon has not yet been defined in any organism. To determine the Yersinia IscR regulon and identify IscR-dependent functions important for virulence, we employed chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of Y. pseudotuberculosis expressing or lacking iscR following iron starvation conditions, such as those encountered during infection. We found that IscR binds to the promoters of genes involved in iron homeostasis, reactive oxygen species metabolism, and cell envelope remodeling and regulates expression of these genes in response to iron depletion. Consistent with our previous work, we also found that IscR binds in vivo to the promoter of the Ysc type III secretion system (T3SS) master regulator LcrF, leading to regulation of T3SS genes. Interestingly, comparative genomic analysis suggested over 93% of IscR binding sites were conserved between Y. pseudotuberculosis and the related plague agent Yersinia pestis. Surprisingly, we found that the IscR positively regulated sufABCDSE Fe-S cluster biogenesis pathway was required for T3SS activity. These data suggest that IscR regulates the T3SS in Yersinia through maturation of an Fe-S cluster protein critical for type III secretion, in addition to its known role in activating T3SS genes through LcrF. Altogether, our study shows that iron starvation triggers IscR to coregulate multiple, distinct pathways relevant to promoting bacterial survival during infection. IMPORTANCE How bacteria adapt to the changing environment within the host is critical for their ability to survive and cause disease. For example, the mammalian host severely restricts iron availability to limit bacterial growth, referred to as nutritional immunity. Here, we show that pathogenic Yersinia use the iron-sulfur (Fe-S) cluster regulator IscR, a factor critical for pathogenesis, to sense iron availability and regulate multiple pathways known or predicted to contribute to virulence. Under low iron conditions that mimic those Yersinia encounter during infection, IscR levels increase, leading to modulation of genes involved in iron metabolism, stress resistance, cell envelope remodeling, and subversion of host defenses. These data suggest that IscR senses nutritional immunity to coordinate processes important for bacterial survival within the mammalian host.
Modelling performance with exponential functions in elite short-track speed skaters

ABSTRACT Mathematical models are used to describe and predict the effects of training on performance. The initial models are structured by impulse-type transfer functions, however, cellular adaptations induced by exercise may exhibit exponential kinetics for their growth and subsequent dissipation. Accumulation of exercise bouts counteracts dissipation and progressively induces structural and functional changes leading to performance improvement. This study examined the suitability of a model with exponential terms (Exp-Model) in elite short-track speed (ST) skaters. Training loads and performance evolution from fifteen athletes (10 males, 5 females) were previously collected over a 3-month training period. Here, we computed the relationship between training loads and performance with Exp-Model and compared with previous results obtained with a variable dose-response model (Imp-Model). Exp-Model showed a higher correlation between actual and modelled performances (R2 = 0.83 ± 0.08 and 0.76 ± 0.07 for Exp-Model and Imp-Model, respectively). Concerning model parameters, a higher (time constant for growth) value was found (p = 0.0047; d = 1.4; 95% CI [0.4;1.9]) in males compared to females with Exp-model, suggesting that females have a faster adaptative response to training loads. Thus, according to this study, Exp-model may better describe training adaptations in elite ST athletes than Imp-Model.
Mesoglycan connects Syndecan‐4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro

Mesoglycan is a mixture of glycosaminoglycans (GAG) with fibrinolytic effects and the potential to enhance skin wound repair. Here, we have used endothelial cells isolated from wild‐type (WT) and Syndecan‐4 null (Sdc4‐/‐) C57BL/6 mice to demonstrate that mesoglycan promotes cell motility and in vitro angiogenesis acting on the co‐receptor Syndecan‐4 (SDC4). This latter is known to participate in the formation and release of extracellular vesicles (EVs). We characterized EVs released by HUVECs and assessed their effect on angiogenesis. Particularly, we focused on Annexin A1 (ANXA1) containing EVs, since they may contribute to tube formation via interactions with Formyl peptide receptors (FPRs). In our model, the bond ANXA1‐FPRs stimulates the release of vascular endothelial growth factor (VEGF‐A) that interacts with vascular endothelial receptor‐2 (VEGFR2) and activates the pathway enhancing cell motility in an autocrine manner, as shown by wound healing/invasion assays, and the induction of endothelial to mesenchymal transition (EndMT). Thus, we have shown for the first time that mesoglycan exerts its pro‐angiogenic effects in the healing process triggering the activation of the three interconnected molecular axis: mesoglycan‐SDC4, EVs‐ANXA1‐FPRs, and VEGF‐A‐VEGFR2.
The impact of the COVID-19 pandemic on mental health among healthcare workers in ear-nose-throat clinics.

INTRODUCTION During the first wave of the COVID-19 pandemic, it was established that otorhinolaryngologists were at a high risk of contracting the infection due to examinations of the upper airways. The aim of this study was to evaluate the impact of the COVID-19 pandemic on mental health among healthcare workers (HCWs) in primary ear-nose-throat (ENT) practices. METHODS This was a cross-sectional questionnaire study among HCWs assessing symptoms of anxiety (Generalized Anxiety Disorder, ten-item scale) and depression (Patients Health Questionnaire, nine-item scale). The survey targeted otolaryngologists and staff in primary private practices in the Capital Region of Denmark during the COVID-19 lock-down in May 2020. RESULTS For 30% of the participants, signs were observed of depressive symptoms and 13% had signs of anxiety symptoms. Seventy percent felt sufficiently protected by their available personal protective equipment. Fifty-two percent worried about becoming infected in relation to their work and 56% feared infecting their families. CONCLUSIONS HCWs in Danish primary ENT practices did not display extraordinary stress reactions during the first wave of the pandemic. Noticeably, participants were concerned about acquiring the infection or transmitting it to their household. FUNDING none. TRIAL REGISTRATION not relevant.
Distinct expression requirements and rescue strategies for BEST1 loss- and gain-of-function mutations

Genetic mutation of the human BEST1 gene, which encodes a Ca2+-activated Cl- channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca2+-dependent Cl- currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that BEST1 patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development, and suggesting that some of the previously classified autosomal dominant mutations actually behave in a dominant-negative manner. Importantly, the strong dominant effect of BEST1 gain-of-function mutations prohibits the restoration of BEST1-dependent Cl- currents in RPE cells by gene augmentation, in contrast to the efficient rescue of loss-of-function mutations via the same approach. Moreover, we demonstrate that gain-of-function mutations are rescuable by a combination of gene augmentation with CRISPR/Cas9-mediated knockdown of endogenous BEST1 expression, providing a universal treatment strategy for all bestrophinopathy patients regardless of their mutation types.
Are Emotions Natural Kinds After All? Rethinking the Issue of Response Coherence

The synchronized co-activation of multiple responses—motivational, behavioral, and physiological—has been taken as a defining feature of emotion. Such response coherence has been observed inconsistently however, and this has led some to view emotion programs as lacking biological reality. Yet, response coherence is not always expected or desirable if an emotion program is to carry out its adaptive function. Rather, the hallmark of emotion is the capacity to orchestrate multiple mechanisms adaptively—responses will co-activate in stereotypical fashion or not depending on how the emotion orchestrator interacts with the situation. Nevertheless, might responses cohere in the general case where input variables are specified minimally? Here we focus on shame as a case study. We measure participants’ responses regarding each of 27 socially devalued actions and personal characteristics. We observe internal and external coherence: The intensities of felt shame and of various motivations of shame (hiding, lying, destroying evidence, and threatening witnesses) vary in proportion (i) to one another, and (ii) to the degree to which audiences devalue the disgraced individual—the threat shame defends against. These responses cohere both within and between the United States and India. Further, alternative explanations involving the low-level variable of arousal do not seem to account for these results, suggesting that coherence is imparted by a shame system. These findings indicate that coherence can be observed at multiple levels and raise the possibility that emotion programs orchestrate responses, even in those situations where coherence is low.
Altered resting‐state functional network connectivity in profound sensorineural hearing loss infants within an early sensitive period: A group ICA study

Data from both animal models and deaf children provide evidence for that the maturation of auditory cortex has a sensitive period during the first 2–4 years of life. During this period, the auditory stimulation can affect the development of cortical function to the greatest extent. Thus far, little is known about the brain development trajectory after early auditory deprivation within this period. In this study, independent component analysis (ICA) technique was used to detect the characteristics of brain network development in children with bilateral profound sensorineural hearing loss (SNHL) before 3 years old. Seven resting‐state networks (RSN) were identified in 50 SNHL and 36 healthy controls using ICA method, and further their intra‐and inter‐network functional connectivity (FC) were compared between two groups. Compared with the control group, SNHL group showed decreased FC within default mode network, while enhanced FC within auditory network (AUN) and salience network. No significant changes in FC were found in the visual network (VN) and sensorimotor network (SMN). Furthermore, the inter‐network FC between SMN and AUN, frontal network and AUN, SMN and VN, frontal network and VN were significantly increased in SNHL group. The results implicate that the loss and the compensatory reorganization of brain network FC coexist in SNHL infants. It provides a network basis for understanding the brain development trajectory after hearing loss within early sensitive period.