bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRX haploinsufficiency compromises photoreceptor precursor translocation and differentiation in human retinal organoids
Authors: Pan Deng , Zhang Xiao , Jin Kangxin , Jin Zi-Bing 
Published: December 2023

Abstract
Background
The CRX-associated autosomal dominant retinopathies suggest a possible pathogenic mechanism of gene haploinsufficiency. However, based on reported human patient cases and studies with mouse models, it is hard to confirm the specific weight of haploinsufficiency in pathogenesis due to the interspecies gaps between gene expression and function.

Methods
We created monoallelic CRX by replacing one allele with tdTomato in human embryonic stem cells (hESCs) and subsequently dissect pathogenesis in hESCs-derived retinal organoids. We used transcriptome and immunofluorescence analyses to dissect phenotypic differences between CRX-monoallelic knockout and control wildtype organoids. For location analysis of CRX+ cells, a CRX-expression-tracing system was constructed in control hESCs. We implemented long-term live-cell imaging to describe the translocation of CRX+ cells between two groups in early organoid differentiation. The expression pattern of these dynamic differences was validated using RNA-seq and immunofluorescence assays.

Results
We identified delayed differentiation of outer nuclear layer (ONL) stratification along with thinner ONL, serious loss of photoreceptor outer segments, as well as downregulated expression of gene for phototransduction and inner/outer segment formation. By live-cell imaging and immunostaining, we observed the overtension of actomyosin network and the arrested translocation of monoallelic CRX+ cells in the early stage of retinal differentiation.

Conclusions
We confirmed that gene haploinsufficiency is the mechanism for the dominant pathogenicity of CRX and discovered that CRX regulated postmitotic photoreceptor precursor translocation in addition to its specification of photoreceptor cell fates during human retinal development. These findings revealed a new underlying mechanism of CRX dominant pathogenesis and provided a new clue for the treatment of CRX-associated human retinopathies.
Patterns and outcomes of health-care associated infections in the medical wards at Bugando medical centre: a longitudinal cohort study
Authors: Kassam Maliha I. , Silago Vitus , Damiano Prisca , Wajanga Bahati , Seni Jeremiah , Mshana Stephen E. , Kalluvya Samuel 
Published: December 2023

Abstract
Background
The burden of healthcare associated infections (HCAIs) in low- and middle-income countries (LMICs) remains underestimated due to diagnostic complexity and lack of quality surveillance systems. We designed this study to determine clinical diagnosis, laboratory-confirmed, associated factors and risks of HCAIs.

Methods
This hospital-based longitudinal cohort study was conducted between March and June 2022 among adults (≥ 18 years) admitted in medical wards at BMC in Mwanza, Tanzania. Patients who were negative for HCAIs by clinical evaluations and laboratory investigations during admission were enrolled and followed-up until discharge or death. Clinical samples were collected from patients with clinical diagnosis of HCAIs for conventional culture and antimicrobial sensitivity testing.

Results
A total of 350 adult patients with a median [IQR] age of 54 [38–68] years were enrolled in the study. Males accounted for 54.6% (n = 191). The prevalence of clinically diagnosed HCAIs was 8.6% (30/350) of which 26.7% (8/30) had laboratory-confirmed HCAIs by a positive culture. Central-line-associated bloodstream infection (43.3%; 13/30) and catheter-associated urinary tract infection (36.7%; 11/30) were the most common HCAIs. Older age was the only factor associated with development of HCAIs [mean (± SD); [95%CI]: 58.9(± 12.5); [54.2–63.5] vs. 51.5(± 19.1); [49.4–53.6] years; p = 0.0391) and HCAIs increased the length of hospital stay [mean (± SD); [95%CI]: 13.8 (± 3.4); [12.5–15.1] vs. 4.5 (± 1.7); [4.3–4.7] days; p < 0.0001].

Conclusion
We observed a low prevalence of HCAIs among adult patients admitted to medical wards in our setting. Central-line-associated bloodstream infections and catheter-associated urinary tract infections are common HCAIs. Significantly, older patients are at higher risk of acquiring HCAIs as well as patients with HCAIs had long duration of hospital stays.
“The COVID-19 pandemic and operational challenges, impacts, and lessons learned: a multi-methods study of U.S. prison systems”
Authors: Novisky Meghan A. , Tostlebe Jennifer , Pyrooz David , Sanchez Jose Antonio 
Published: December 2023

Abstract
Background
The purpose of this study was to examine how the COVID-19 pandemic changed U.S. prison operations and influenced the daily work of prison staff.

Methods
In collaboration with the National Institute of Corrections, we administered a survey to 31 state correctional agencies in April 2021 and conducted five focus groups with 62 correctional staff.

Results
Using a framework of bounded rationality, we find that daily operations were strained, particularly in the areas of staffing, implementing public health policy efforts, and sustaining correctional programming. While prison systems and staff were under-prepared to respond to the pandemic, they attempted to address complex problems with the limited resources they had.

Conclusions
Results underscore a need in corrections for prioritizing further developments and reviews of collaborative policies and practices for managing crisis situations. Seeking avenues for leveraging technological innovations to improve operations and facilitate enhanced communication are especially warranted. Finally, meaningful reductions in the prison population, changes in physical infrastructure, and expansions of hiring and retention initiatives are critical for positioning prisons to manage future emergencies.
Soft‐tissue tension during total hip arthroplasty measured in four patients and predicted using a musculoskeletal model
Authors: Higa Masaru , Tanino Hiromasa , Ito Hiroshi , Banks Scott A. 
Published: December 2023

AbstractPurposeSoft‐tissue tension around the hip joint is related to the incidence of dislocation after total hip arthroplasty (THA), but it remains difficult to quantify the soft‐tissue tension during surgery. In this study, a three‐dimensional force sensor‐instrumented modular femoral head was developed and used to quantify soft‐tissue tension during THA. The forces at the hip joint were also calculated using a three‐dimensional musculoskeletal computer model to validate the measured forces.MethodsSoft‐tissue tension was investigated by measuring the hip joint forces and directions during intraoperative trialing in four patients through passive range of motion (ROM) from 0° extension to 90° flexion. A musculoskeletal model with THA, which was scaled to one of four patients, was developed. The hip joint forces were calculated under the same motion.ResultsThrough the passive ROM, the magnitude of soft‐tissue tension was greatest when the hip was extended, decreased with flexion to 34°, and progressively increased to flexion at 90°. The mediolateral force component was relatively constant, but the supero‐inferior and anterior–posterior force components changed significantly. Within‐individual variations were small during three repeated cycles of measurement, but magnitudes varied significantly among patients. Similar force patterns and magnitudes were calculated by the musculoskeletal model.ConclusionsThis study demonstrates that it is possible to quantify soft‐tissue tension and direction during THA with an instrumented head. There was general agreement between the calculated and measured forces in both pattern and magnitude. Including additional subject‐specific details would further enhance agreement between the model and measured hip forces.
Behavioural relevance of redundant and synergistic stimulus information between functionally connected neurons in mouse auditory cortex
Authors: Koçillari Loren , Celotto Marco , Francis Nikolas A. , Mukherjee Shoutik , Babadi Behtash , Kanold Patrick O. , Panzeri Stefano 
Published: December 2023

AbstractMeasures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity—that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations.
Elevation of tacrolimus concentration after administration of methotrexate for treatment of graft-versus-host disease in pediatric patients received allogeneic hematopoietic stem cell transplantation
Authors: Inoue Chiaki , Yamamoto Takehito , Miyata Hiroshi , Suzuki Hiroshi , Takada Tappei 
Published: December 2023

Abstract
Background
Methotrexate (MTX) is used to treat graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, a case was encountered in which the blood concentration of tacrolimus (TCR) at steady state increased after intravenous MTX administration for GVHD treatment (therapeutic IV-MTX administration). Therefore, this study aimed to investigate the effect of therapeutic IV-MTX administration on the pharmacokinetics of TCR.

Methods
This single-center, retrospective, observational study included patients who underwent allo-HSCT and received therapeutic IV-MTX administration during immunosuppressive therapy with continuous intravenous infusion (CIV) of TCR from April 2004 to December 2021. Here, each therapeutic IV-MTX administration was defined as a case and independently subjected to subsequent analyses. The blood concentration of TCR at steady state (Css), ratio of Css to daily TCR dose (C/D), and clinical laboratory data were compared before and after therapeutic IV-MTX administration. In addition, dose changes in the TCR after therapeutic IV-MTX administration were evaluated.

Results
Ten patients (23 cases) were included in this study. The C/D value significantly increased after therapeutic IV-MTX administration (median: 697 vs. 771 (ng/mL)/(mg/kg), 1.16-fold increase, P < 0.05), indicating a reduction in the apparent clearance of TCR. Along with the increase in C/D, significant increases were observed in aspartate transaminase level (median: 51.0 vs. 92.9 U/L, P < 0.01) and alanine aminotransferase level (median: 74.5 vs. 99.4 U/L, P < 0.01) indicating that liver injury after therapeutic IV-MTX administration contributes to the observed C/D increase. In addition, the daily dose of TCR was reduced in 11 cases (47.8%) after therapeutic IV-MTX administration, and the relative frequency of dose reduction tended to be higher than that of dose increase (median: 37.5% vs. 0.0%, P = 0.0519, permuted Brunner-Munzel test). The magnitude of dose reduction was 18.8% (7.4–50.0%) in the 11 cases with dose reduction.

Conclusions
Therapeutic IV-MTX administration cause a significant increase in C/D, which requires TCR dose reduction. Careful therapeutic drug monitoring of TCR is needed after therapeutic IV-MTX administration in patients receiving immunosuppressive therapy with TCR after allo-HSCT.
Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells
Authors: Cha Seung-Gyu , Rhim Won-Kyu , Kim Jun Yong , Lee Eun Hye , Lee Seung Yeon , Park Jeong Min , Lee Jeoung Eun , Yoon Hyeji , Park Chun Gwon , Kim Bum Soo , Kwon Tae Gyun , Lee Youngmi , Lee Dong Ryul , Han Dong Keun 
Published: December 2023

Abstract

Background
To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation.

Methods

We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH)
2
(M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform. Additionally, we utilized differentiating extracellular vesicles (dEV) isolated during intermediate mesoderm differentiation into kidney progenitor cells, and IM cells were serially incorporated to facilitate kidney tissue regeneration through their differentiation into kidney progenitor cells in the 3/4 nephrectomy mouse model.

Results
The use of differentiating extracellular vesicles facilitated IM differentiation into kidney progenitor cells without additional differentiation factors. This led to improvements in various regeneration-related bioactivities including tubule and podocyte regeneration, anti-fibrosis, angiogenesis, and anti-inflammation. Finally, implanting PMEZ/dEV/IM scaffolds in mouse injury model resulted in the restoration of kidney function.

Conclusions
Our study has demonstrated that utilizing biodegradable PLGA-based scaffolds, which include multipotent cells capable of differentiating into various kidney progenitor cells along with supporting components, can facilitate kidney tissue regeneration in the mouse model that simulates CKD through 3/4 nephrectomy.

Graphical Abstract
Teleophthalmology and retina: a review of current tools, pathways and services
Authors: Than Jonathan , Sim Peng Y. , Muttuvelu Danson , Ferraz Daniel , Koh Victor , Kang Swan , Huemer Josef 
Published: December 2023

AbstractTelemedicine, the use of telecommunication and information technology to deliver healthcare remotely, has evolved beyond recognition since its inception in the 1970s. Advances in telecommunication infrastructure, the advent of the Internet, exponential growth in computing power and associated computer-aided diagnosis, and medical imaging developments have created an environment where telemedicine is more accessible and capable than ever before, particularly in the field of ophthalmology. Ever-increasing global demand for ophthalmic services due to population growth and ageing together with insufficient supply of ophthalmologists requires new models of healthcare provision integrating telemedicine to meet present day challenges, with the recent COVID-19 pandemic providing the catalyst for the widespread adoption and acceptance of teleophthalmology. In this review we discuss the history, present and future application of telemedicine within the field of ophthalmology, and specifically retinal disease. We consider the strengths and limitations of teleophthalmology, its role in screening, community and hospital management of retinal disease, patient and clinician attitudes, and barriers to its adoption.
APACHE IV, SAPS III, and SOFA scores for outcome prediction in a surgical/trauma critical care unit: an analytical cross-sectional study
Authors: Ghazaly Huda F. , Aly Ahmed Alsaied A. , Sayed Marwa H. , Hassan Mahmoud M. 
Published: December 2023

Abstract
Background
Patients’ outcomes in surgical/trauma intensive care units (ICUs) are still challenging to predict. There has been a lack of consensus over the efficacy of Acute Physiology and Chronic Health Evaluation IV (APACHE IV), Simplified Acute Physiology Score III (SAPS III), and Sequential Organ Failure Assessment (SOFA) scores in predicting patient outcomes. This analytical cross-sectional study was designed to determine how well APACHE IV, SAPS III, and SOFA scores predict ICU mortality and the length of stay in a surgical ICU. APACHE IV, SAPS III, and SOFA scores were calculated on admission. The effectiveness of these scores in predicting mortality was determined using logistic regression models. The accuracy of these discriminative abilities was measured using the area under the receiver operating characteristic curve (AUC). The Hosmer and Lemeshow calibration test was calculated to test the model fit. The agreement between APACHE IV, SAPS III, and SOFA scores in the prediction of mortality was examined using the Bland–Altman curve.

Results
A total of 148 patients met the study criteria. APACHE IV was the only significant predictor of mortality, with a 1-point increase in the APACHE IV score resulting in a 5% increase in death probability (AOR = 1.049, 95% CI 1.028–1.069) (P-value < 0.001). The APACHE IV score was superior to the SAPS III and SOFA scores regarding accuracy, with an AUC of 0.766 (95% CI, 0.670–0.862) (P-value < 0.001). Furthermore, there was a significant positive correlation between APACHE IV score and ICU length of stay (r = 0.22, P = 0.004).

Conclusion
APACHE IV outperformed SAPS III and SOFA scores in predicting mortality in a surgical/trauma critical care unit and showed a significant positive correlation with the ICU length of stay.
The ankyrin repeat-containing protein PlANK1 mediates mycelial growth, oospore development, and virulence in Peronophythora litchii
Authors: Situ Junjian , Zhang Xinning , Zhou Xiaofan , Zhang Zijing , Xi Pinggen , Kong Guanghui , Jiang Zide 
Published: December 2023

AbstractLitchi downy blight, caused by Peronophythora litchii, is one of the most serious diseases in major litchi-producing regions worldwide. The ankyrin (ANK) repeat is one of the most common protein-protein interaction motifs found in all kingdoms of life proteins. ANK-containing proteins have been demonstrated to regulate various biological processes in animals, plants, and fungi. However, their functions in phytopathogenic oomycetes remain unknown. Here, we identified 284 non-redundant genes that encode ANK-containing proteins in P. litchii and classified them into 11 subfamilies. Among them, PlANK1 was found to be highly up-regulated in oospores and from zoospores to the infection process. Loss of PlANK1 in P. litchii resulted in impaired mycelial growth and cyst germination, accelerated zoospore encystment, and increased sensitivity to hyperosmotic stresses and Congo red. Furthermore, PlANK1 deletion mutants were defective in oospore formation and development. Inoculation assays showed that the absence of PlANK1 severely diminished the pathogen’s virulence on litchi leaf and fruit. Through transcriptome analysis and nitrogen source utilization assays, we demonstrated that PlANK1 modulates the pathogen’s nitrogen metabolism. Altogether, our findings indicate that PlANK1 is a key regulator of sexual and asexual development, and virulence in P. litchii.
Mothers’ personality and children with feeding and eating disorders: a nested case–control study
Authors: Al Agroudi Aml Al Marzouki , Rashed Ibrahem Hamdey , Yahia Sohier , Tobar Salwa 
Published: December 2023

Abstract
Background
Feeding and eating disorders are major factors in nutrition problems. Mothers have a big role in shaping feeding and eating behaviors. This study aimed at estimating the prevalence of feeding and eating disorders among children in pediatric outpatient clinics (6–12 years old) and comparing personality factors among mothers of children with feeding and eating disorders versus those without feeding and eating disorders.

Results
This study included 528 children who were screened for feeding and eating disorders using the DSM-5. For the detected children, their mothers’ personalities were assessed using Cattell’s 16 personality factor test after history was taken using a child psychiatric sheet. The resulting prevalence of feeding and eating disorders is 13%, and the major mother’s personality factor that contributed is the control factor.

Conclusions
Certain personality factors of the studied mothers (controlled, tender-minded, imaginative, forthright, and apprehensive) correlate with the prevalence of feeding and eating disorders among their children, compared with those without feeding and eating disorders. Mothers’ personalities should be assessed in children with feeding and eating disorders, especially when these factors seem likely.
Comparative effects of patient-specific 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy
Authors: Mahmood Hassan , Rafique Saba , Waheed Aleena , Sabir Nimra , Hussain Ghazal 
Published: December 2023

Abstract
Background
Low back pain (LBP) resides as a most common type of symptom pointing towards lumber radiculopathy. It is defined as burning sharp leg pain that originates from the back and goes all the way down your legs and extends into the toes and foot. Lumbosacral radiculopathy is caused by pathology of the intervertebral disk or associated structures. Different dimensional traction has been used to treat lumbar radiculopathy. This study aimed to compare the effects of 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy. The randomized clinical trial study of 4 weeks was carried out at the Lifeline Health Care Imaging and Pain Center and the Hamza Hospital Lahore. Twenty-six subjects were included in the clinical trial and divided into two groups after randomization. Group A received three-dimensional lumbar traction with traction force 50% of total body weight on Spine MT 3D traction machine, and group B received two-dimensional lumbar traction with traction force 50% of total body weight. Pre- and post-values of NPRS and ODI were noted.

Results
Parametric tests were used during statistical analysis because data was normally distributed. NPRS pre- and posttreatment values showed significant results with p-value < 0.05. ODI pre- and post-values were also obvious with p-value < 0.05. Independent sample T-test was used to assess across the group comparison, suggesting that both groups showed significant improvements of NPRS and ODI post-treatment with p-value (< 0.001).

Conclusion
The study concluded that 3D traction significantly reduced pain levels and improved functional impairment more effectively than 2D traction in patients with lumbar radiculopathy.

Trial registration
Trial was registered with ClinicalTrials.gov: NCT05356689.