bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case report of paraneoplastic bullous pemphigoid associated with mantle cell lymphoma: A rare presentation
Authors: Md Radzi Ahmad Bakhtiar , Kasim Sazzli Shahlan 
Published: February 2023

Rationale:
We report a rare case of paraneoplastic bullous pemphigoid associated with mantle cell lymphoma.

Patients concerns:
The patient presented with 5 months’ history of generalized skin itchiness, night sweat and loss of weight. The skin manifestations started over the foot and hand area. However, he started to developed tense blisters over the face, trunk and limbs 3 days prior to this admission.

Diagnoses:
The skin biopsy report showed subepidermal bullae, in which the immunofluorescence findings in keeping with bullous pemphigoid. The peripheral blood immunophenotyping was suggestive of mantle cell lymphoma. Hence, a diagnosis of paraneoplastic bullous pemphigoid associated with mantle cell lymphoma was made.

Interventions:
The patient was initiated with a cytoreduction chemotherapy.

Outcomes:
Unfortunately, patient’s condition deteriorated further due to neutropenic sepsis and he succumbed after 2 weeks of intensive care.

Lessons:
Bullous pemphigoid associated with mantle cell lymphoma are very rare. The presentation of bullous pemphigoid led to the detection of mantle cell lymphoma. Early diagnosis and appropriate treatment is crucial in managing this aggressive type of the disease. Both, bullous pemphigoid and mantle cell lymphoma had a parallel clinical course which suggests a paraneoplastic phenomenon in this reported case.
Confirmation of theMIR204n.37C>T heterozygous variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma
Authors: Jedlickova J. , Vajter M. , Barta T. , Black G. , Mares J. , Fichtl M. , Kousal B. , Dudakova L. , Liskova P. 
Published: February 2023

ABSTRACTFour members of a three-generation family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T inMIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change inMIR204. The chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, family members were shown to be affected by albinism resulting from biallelic pathogenicOCA2variants.
Collaborative Clinical Reasoning: a scoping review
Authors: Lee Ching-Yi , Lai Hung-Yi , Lee Ching-Hsin , Chen Mi-Mi , Yau Sze-Yuen 
Published: February 2023

AbstractIntroductionTeam approaches in healthcare highlight the importance and benefits of collaboration on maximising clinical outcomes and patient safety. Based on extant literature, the authors aimed to explore collaborative clinical reasoning (CCR) among healthcare professionals.MethodsA scoping review was undertaken to examine CCR related studies in healthcare. Medline, PsychInfo, SciVerse Scopus, and Web of Science were searched. Inclusion criteria included full-text articles published between 2011 to 2020. Search terms included cooperative, collaborative, shared, team, collective, reasoning, problem solving, decision making, combined with clinical or medicine or medical, but excluded shared decision making.ResultsA total of 24 articles were identified in the review. Analysis of the articles resulted in four major content themes: (1) Decision-making process (n=14); (2) Quality assessment by MDTs-MODe (Multidisciplinary Team-Metric for the Observation of Decision Making; n=5) (3) CCR theory and definitions(n=3); and (4) Problem-solving process (n=2). Most articles focused on communication associated with collaborative decision-making processes. The discussion of team impacts among all studies was merely the notion of clinical reasoning as an essential component of the collaborative or interprofessional practice. None provided direct evidence on the process of CCR or its impact on clinical outcomes. Only two articles provided specific definitions on CCR.DiscussionWe illuminate the necessity of further research in CCR, specifically with a focus on cognitive components of CCR. A better understanding of current CCR research in healthcare may inform future discussions around establishing strategies to enhance CCR development, and hence provide positive influence on medical education and patient safety.
Combining organotypic tissue culture with multi-color fluorescence light-sheet microscopy (OTCxLSFM) – a novel tool to study glioma invasion/migration
Authors: Haydo Alicia , Wehle Andrej , Herold-Mende Christel , Kögel Donat , Pampaloni Francesco , Linder Benedikt 
Published: February 2023

AbstractGlioblastoma is a very aggressive tumor and represents the most common primary brain malignancy. Key characteristics include its high resistance against conventional treatments, such as radio- and chemotherapy and its diffuse tissue infiltration, preventing complete surgical resection. The analysis of migration and invasion processes in a physiological microenvironment allows for enhanced understanding of these processes and can lead to improved therapeutic approaches. Here, we combine two state-of-the-art techniques, adult organotypic brain tissue slice culture (OTC) and light sheet fluorescence microscopy (LSFM) of cleared tissues in a combined method termed OTCxLSFM. Using this methodology, we can show that glioblastoma tissue infiltration can be effectively blocked through treatment with arsenic trioxide, as well as genetic depletion of the tetraspanin, transmembrane receptor CD9. With our analysis-pipeline we gain single-cell level, three-dimensional information, as well as insights into the morphological appearance of the tumor cells.
Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
Authors: Yin Kailin , Peluso Michael J. , Luo Xiaoyu , Thomas Reuben , Shin Min-Gyoung , Neidleman Jason , Andrew Alicer , Young Kyrlia , Ma Tongcui , Hoh Rebecca , Anglin Khamal , Huang Beatrice , Argueta Urania , Lopez Monica , Valdivieso Daisy , Asare Kofi , Deveau Tyler-Marie , Munter Sadie E. , Ibrahim Rania , Ständker Ludger , Lu Scott , Goldberg Sarah A. , Lee Sulggi A. , Lynch Kara L. , Kelly J. Daniel , Martin Jeffrey N. , Münch Jan , Deeks Steven G. , Henrich Timothy J. , Roan Nadia R. 
Published: February 2023

AbstractLong COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple “omics” assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.
Childhood cognitive ability and self-harm and suicide in later life
Authors: Iveson Matthew H. , Ball Emily L. , Whalley Heather C. , Deary Ian J. , Cox Simon R. , Batty G. David , John Ann , McIntosh Andrew M. 
Published: February 2023

AbstractSelf-harm and suicide remain prevalent in later life. For younger adults, work has highlighted an association between higher early-life cognitive ability and lower self-harm and suicide risk. Comparatively little is known about its association with self-harm and suicide among older adults. Furthermore, most work has measured cognitive ability in early adulthood, raising issues of potential confounding by emerging psychiatric conditions.The present study examined the association between childhood (age 11) cognitive ability and self-harm and suicide risk among a Scotland-wide cohort of older adults (N = 53037), using health data linkage to follow individuals from age 34 to 85. Self-harm events were extracted from hospital admissions and suicide deaths were extracted from national mortality records. Multistate models were used to model transitions between unaffected, self-harm, and then suicide or non-suicide death, and to examine the association between childhood cognitive ability and each transition.After adjusting for childhood and adulthood socioeconomic conditions, higher childhood cognitive ability was significantly associated with reduced risk of self-harm among older females (N events = 516; HR = 0.90, 95% CI = [0.81, 0.99]). A similar, though non-significant, association was observed among older males (N events = 451; HR = 0.90, 95% CI = [0.82, 1.00]). Although suicide risk was higher among older adults experiencing self-harm, childhood cognitive ability was not significantly associated with suicide risk among either older adults experiencing no self-harm events (Male: N events = 118, HR = 1.17, 95% CI = [0.84, 1.63]; Female: N events = 31, HR = 1.30, 95% CI = [0.70, 2.41]) or those experiencing a self-harm event during follow-up (Male: N events = 16, HR = 1.05, 95% CI = [0.61, 1.80]; Female: N events = 13, HR = 1.08, 95% CI = [0.55, 2.14]). Higher suicide risk was significantly associated with covariates including higher adulthood deprivation and longer time in the self-harm state. These results extend work on cognitive ability and mental health, demonstrating that these associations can span across the life course and into older age.
Maternal adverse childhood experiences on child growth and development in rural Pakistan: an observational cohort study
Authors: Chung Esther O. , Scherer Elissa , LeMasters Katherine , Bates Lisa , Hagaman Ashley , Staley Brooke S. , Zalla Lauren , Sikander Siham , Maselko Joanna 
Published: February 2023

AbstractMaternal adverse childhood experiences (ACEs) have been associated with negative impacts on children. However, not all types or levels of adversity are similarly deleterious and research from diverse contexts is needed to better understand why and how intergenerational transmission of adversity occurs. We examined the role of maternal ACEs on child growth and development at 36 months postpartum in rural Pakistan. We used data from 877 mother-child dyads in the Bachpan Cohort, a birth cohort study. Maternal ACEs were captured using an adapted version of the ACE- International Questionnaire. Outcomes included child growth, fine motor and receptive language development, and socioemotional and behavioral development at 36 months of age. To estimate the associations between maternal ACEs and child outcomes, we used multivariable generalized linear models with inverse probability weights to account for sampling and loss to follow-up. Over half of mothers in our sample (58%) experienced at least one ACE. Emotional abuse, physical abuse, and emotional neglect were the most commonly reported. We found null relationships between the number of maternal ACEs and child growth. Maternal ACEs were associated with higher fine motor and receptive language development and worse socioemotional and behavioral outcomes. Maternal ACE domains had similarly varying relationships with child outcomes. Our findings highlight the complexity of intergenerational associations between maternal ACEs and children’s growth and development. Further work is necessary to examine these relationships across cultural contexts and identify moderating factors to mitigate potential negative intergenerational effects.
Public toilets have reduced enteric pathogen hazards in San Francisco
Authors: Barker Troy , Capone Drew , Amato Heather K. , Clark Ryan , Henderson Abigail , Holcomb David A. , Kim Elizabeth , Pape Jillian , Parker Emily , VanderYacht Thomas , Graham Jay , Brown Joe 
Published: February 2023

ABSTRACTUncontained fecal wastes in cities may present exposure risks to the public. We collected discarded feces from public spaces in San Francisco for analysis by RT-qPCR for a range of enteric pathogens. Out of 59 samples, we found 12 (20%) were of human origin and 47 (80%) were non-human; 30 of 59 stools were positive for ≥1 of the 35 pathogens assessed, including pathogenicE. coli, Shigella, norovirus,Cryptosporidium, andTrichuris. Using quantitative enteric pathogen estimates and data on observed fecal waste from a public reporting system, we modeled pathogens removed from the environment attributable to a recently implemented program of public toilet construction. We estimated that each new public toilet reduced the annual number of enteric pathogens released into the immediate environment (within 500 m walking distance), including 6.3 × 1012enteropathogenicE. coli(95% CI: 4.0 × 1012– 7.9 × 1012), 3.2 × 1011enteroaggregativeE. coli(95% CI: 1.3 × 1011– 6.3 × 1011), and 3.2 × 108Shigella(6.3 × 107– 2.5 × 109). Improving access to public sanitation can reduce enteric pathogen hazards in cities. Interventions must also consider the hygienic disposal of animal waste to reduce microbial hazards with zoonotic infection potential.SYNOPSISThis paper describes enteric pathogen hazards from discarded feces on the streets of San Francisco and estimates their reduction following a public toilet intervention.TOC/Abstract artCreated with BioRender and a photograph by author Jay Graham
Functional investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
Authors: Bhattarai Kashi Raj , Mobley Robert J. , Barnett Kelly R. , Ferguson Daniel C. , Hansen Baranda S. , Diedrich Jonathan D. , Bergeron Brennan P. , Yang Wenjian , Crews Kristine R. , Manring Christopher S. , Jabbour Elias , Paietta Elisabeth , Litzow Mark R. , Kornblau Steven M. , Stock Wendy , Inaba Hiroto , Jeha Sima , Pui Ching-Hon , Cheng Cheng , Pruett-Miller Shondra M. , Relling Mary V. , Yang Jun J. , Evans William E. , Savic Daniel 
Published: February 2023

ABSTRACTAlthough acute lymphoblastic leukemia (ALL) is the most common childhood cancer, there is limited understanding of the contribution of inherited genetic variation on inter-individual differences in chemotherapy response. Defining genetic factors impacting therapy failure can help better predict response and identify drug resistance mechanisms. We therefore mapped inherited noncoding variants associated with chemotherapeutic drug resistance and/or treatment outcome to ALLcis-regulatory elements and investigated their gene regulatory potential and genomic connectivity using massively parallel reporter assays and promoter capture Hi-C, respectively. We identified 53 variants with reproducible allele-specific effects on transcription and high-confidence gene targets. Subsequent functional interrogation of the top variant (rs1247117) determined that it disrupted a PU.1 consensus motif and PU.1 binding affinity. Importantly, deletion of the genomic interval containing rs1247117 sensitized ALL cells to vincristine. Together, these data demonstrate that noncoding regulatory variation associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to chemotherapeutic agents in ALL.
ZEB1 controls a lineage-specific transcriptional program essential for melanoma cell state transitions
Authors: Durand Simon , Tang Yaqi , Pommier Roxane M. , Benboubker Valentin , Grimont Maxime , Boivin Felix , Barbollat-Boutrand Laetitia , Cumunel Eric , Dupeuble Florian , Eberhardt Anaïs , Plaschka Maud , Dalle Stéphane , Caramel Julie 
Published: February 2023

AbstractCell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required. Expression of the ZEB1 transcription factor is frequently activated in melanoma, where it fosters adaptive resistance to targeted therapies. Here, we performed a genome-wide characterization of ZEB1 transcriptional targets, by combining ChIP-sequencing and RNA-sequencing, upon phenotype switching in melanoma models. We identified and validated ZEB1 binding peaks in the promoter of key lineage-specific genes crucial for melanoma cell identity. Mechanistically, ZEB1 negatively regulates SOX10-MITF dependent proliferative/melanocytic programs and positively regulates AP-1 driven invasive and stem-like programs. Comparative analyses with breast carcinoma cells revealed lineage-specific ZEB1 binding, leading to the design of a more reliable melanoma-specific ZEB1 regulon. We then developed single-cell spatial multiplexed analyses to characterize melanoma cell states intra-tumoral heterogeneity in human melanoma samples. Combined with scRNA-Seq analyses, our findings confirmed increased ZEB1 expression in Neural-Crest-like cells and mesenchymal cells, underscoring its significancein vivoin both populations. Overall, our results define ZEB1 as a major transcriptional regulator of cell states transitions and provide a better understanding of lineage-specific transcriptional programs sustaining intra-tumor heterogeneity in melanoma.Graphical Abstract
A targetable N-terminal motif orchestrates α-Synuclein oligomer to fibril conversion
Authors: Santos Jaime , Cuellar Jorge , Pallarès Irantzu , Byrd Emily J , Lends Alons , Moro Fernando , Abdul-Shukkoor Muhammed Bilal , Pujols Jordi , Velasco-Carneros Lorea , Sobott Frank , Otzen Daniel E , Calabrese Antonio N , Muga Arturo , Pedersen Jan S , Loquet Antoine , Valpuesta Jose María , Radford Sheena E , Ventura Salvador 
Published: February 2023

ABSTRACTOligomeric species populated during α-synuclein aggregation are considered key drivers of neurodegeneration in Parkinson’s disease. However, the development of oligomer-targeting therapeutics is constrained by our limited knowledge of their structure and the molecular determinants driving their conversion to fibrils. PSMα3 is a nanomolar peptide binder of α-synuclein oligomers that inhibits aggregation by blocking oligomer to fibril conversion. Here, we investigate the binding of PSMα3 to α-synuclein oligomers to discover the mechanistic basis of this protective activity. We find that PSMα3 selectively targets an α-synuclein N-terminal motif (residues 36-61) that populates a distinct conformation in the monomeric and oligomeric states. This α-synuclein region plays a pivotal role in oligomer to fibril conversion, as its absence renders the central NAC domain insufficient to prompt this structural transition. The hereditary mutation G51D, associated with early-onset Parkinson’s disease, causes a conformational fluctuation in this region, leading to delayed oligomer to fibril conversion and an accumulation of oligomers that are resistant to remodeling by molecular chaperones. Overall, our findings unveil a new targetable region in α-synuclein oligomers, advance our comprehension of oligomer to amyloid fibril conversion and reveal a new facet of α-synuclein pathogenic mutations.
Identification of the aldolase responsible for the production of 22-hydroxy-23,24-bisnorchol-4-ene-3-one from natural sterols inMycolicibacterium smegmatis
Authors: Hernández-Fernández Gabriel , Acedos Miguel G. , García José L. , Galán Beatriz 
Published: February 2023

ABSTRACTMycobacterial mutants blocked in ring degradation constructed to achieve C19 synthons production, also accumulate by-products such as C22 intermediates throughout an alternative pathway reducing the production yields and complicating the downstream purification processing of final products. In this work, we have identified theMSMEG_6561gene, encoding the only aldolase on the chromosome responsible for the transformation of 22-hydroxy-3-oxo-cholest-4-ene-24-carboxyl-CoA (22-OH-BCN-CoA) into the 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) precursor (20S)-3-oxopregn-4-ene-20-carboxaldehyde (3-OPA). The deletion of this gene increases the production yield of the C-19 steroidal synthon 4-androstene-3,17-dione (AD) from natural sterols, avoiding the production of 4-HBC as by-product and the drawbacks in the AD purification. The molar yield of AD production using the MS6039-5941-6561 triple mutant strain was checked in flasks and bioreactor improving very significantly compared with the previously described MS6039-5941 strain.
Mechanical forces at the kidney filtration barrier govern spatial orientation of podocyte processes on capillaries
Authors: Unnersjö-Jess David , Ramdedovic Amer , Butt Linus , Plagmann Ingo , Höhne Martin , Hackl Agnes , Blom Hans , Schermer Bernhard , Benzing Thomas 
Published: February 2023

ABSTRACTMammalian kidneys filter enormous volumes of water and small solutes, a filtration driven by the very high hydrostatic pressure in glomerular capillaries. Interdigitating cellular processes of podocytes form the slits for fluid filtration. They are connected by the membrane-like slit diaphragm cell junction containing a mechanosensitive ion channel complex and allow filtration while counteracting hydrostatic pressure. Using high-resolution microscopy, we show that filtration-slit-generating secondary processes preferentially align along the capillaries’ longitudinal axis while primary processes are preferably perpendicular to the longitudinal direction. The preferential orientation requires maturation in development and is lost in disease states. We demonstrate that loss of proper orientation might contribute to impaired filtration by collapsing of the filtration slits and reducing the mechanical stability of podocyte processes. Together, these data suggest that podocytes sense mechanical strain to utilize circumferential hoop stress balancing the massive mechanical strain generated from fluid flow over the filtration slit.