bluuebunny/crossref_metadata_2025_split huggingface dataset:
The kinase ATR controls meiotic crossover distribution at the genome scale in Arabidopsis
Authors: Zhu Longfei , Dluzewska Julia , Fernández-Jiménez Nadia , Ranjan Rajeev , Pelé Alexandre , Dziegielewski Wojciech , Szymanska-Lejman Maja , Hus Karolina , Górna Julia , Pradillo Mónica , Ziolkowski Piotr A 
Published: October 2024

Abstract
Meiotic crossover, i.e. the reciprocal exchange of chromosome fragments during meiosis, is a key driver of genetic diversity. Crossover is initiated by the formation of programmed DNA double-strand breaks (DSBs). While the role of ATAXIA-TELANGIECTASIA AND RAD3-RELATED (ATR) kinase in DNA damage signaling is well-known, its impact on crossover formation remains understudied. Here, using measurements of recombination at chromosomal intervals and genome-wide crossover mapping, we showed that ATR inactivation in Arabidopsis (Arabidopsis thaliana) leads to dramatic crossover redistribution, with an increase in crossover frequency in chromosome arms and a decrease in pericentromeres. These global changes in crossover placement were not caused by alterations in DSB numbers, which we demonstrated by analyzing phosphorylated H2A.X foci in zygonema. Using the seed-typing technique, we found that hotspot usage remains mainly unchanged in atr mutants compared with wild-type individuals. Moreover, atr showed no change in the number of crossovers caused by two independent pathways, which implies no effect on crossover pathway choice. Analyses of genetic interaction indicate that while the effects of atr are independent of MMS AND UV SENSITIVE81 (MUS81), ZIPPER1 (ZYP1), FANCONI ANEMIA COMPLEMENTATION GROUP M (FANCM), and D2 (FANCD2), the underlying mechanism may be similar between ATR and FANCD2. This study extends our understanding of ATR's role in meiosis, uncovering functions in regulating crossover distribution.
Chemical-sensitized MITOGEN-ACTIVATED PROTEIN KINASE 4 provides insights into its functions in plant growth and immunity
Authors: Zhang Yan , Ge Shating , Dong Lele , Liu Niu , Shao Yiming , Fan Zong , Yang La , Si Qi , Ye Yajin , Ren Dongtao , Zhang Shuqun , Xu Juan 
Published: October 2024

Abstract
Two mitogen-activated protein kinase (MAPK) cascades with MPK4 and MPK3/MPK6 as the bottommost kinases are key to plant growth/development and immune signaling. Disruption of the MPK4 cascade leads to severe dwarfism and autoimmunity, complicating the study of MPK4 in plant growth/development and immunity. In this study, we successfully rescued the Arabidopsis (Arabidopsis thaliana) mpk4 mutant using a chemical-sensitized MPK4 variant, MPK4YG, creating a conditional activity-null mpk4 mutant named MPK4SR (genotype: PMPK4:MPK4YG mpk4) that could be used to examine the functions of MPK4 in plant growth/development and immunity. We discovered that the duration of the loss of MPK4 activity is important to plant immune responses. Short-term loss of MPK4 activity did not impact flg22-induced ROS burst or resistance against Pseudomonas syringae (Pst). Enhanced Pst resistance was only observed in the MPK4SR plants with stunted growth following prolonged inhibition of MPK4 activity. Transcriptome analyses in plants with short-term loss of MPK4 activity revealed a vital role of MPK4 in regulating several housekeeping processes, including mitosis, transcription initiation, and cell wall macromolecule catabolism. Furthermore, the constitutive weak activation of MPK4GA in the MPK4CA plants (genotype: PMPK4:MPK4GA mpk4) led to early flowering and premature senescence, which was associated with its compromised resistance against Pst. These findings suggest that MPK4 plays important roles in plant growth and development and in maintaining the delicate balance between growth/development and immune adaptation in plants.
How to induce honesty: results from a large-scale experiment
Authors: Ho Teck-Hua , Hsu Su-Chin , Jin Lawrence , Kim Dayoung , Kim Jeongbin , Leong Ching 
Published: October 2024

Abstract
Everyday public behavior is premised on honesty. But the imperative to be honest can conflict with self-interest. This conflict between public good and private gain is one of the largest sources of malignity in policymaking, often resulting in noncompliance, inaction, or outright sabotage. This empirical paper examines whether giving the option to be seen as honest helps to reduce malignity in public behavior. We conduct a large field experiment involving 34,543 adults in nine countries to study what drives people to behave more honestly. In a three-arm randomized control trial, subjects reported the outcome from a single roll of an unbiased, six-sided die. The higher the reported value, the more they earned. In two of the arms (“private cash” and “private lottery”), the roll was observed only by the subject. In the third arm (“public cash”), subjects could opt to have their roll observed by the experimenter. A truthful report will yield an average value of 3.5. In the two “private” arms, we found significant overreporting (from 3.76 in China to 4.43 in Mexico). In the “public cash” arm, 85% of subjects opted to be observed, with zero or minimum overreporting (3.46 in Germany, to 3.61 in Indonesia). We develop and estimate a model of honesty that can account for behavioral regularities across the nine countries well. Our study shows that most people want to be seen as honest and a simple policy of providing the additional option of being observed is sufficient to induce them to behave honestly.
A unified theory of risk
Authors: Hirvelä Jaakko , Paterson Niall J 
Published: October 2024

Abstract
A novel theory of comparative risk is developed and defended. Extant theories are criticized for failing the tests of extensional and formal adequacy. A unified diagnosis is proposed: extant theories consider risk to be a univariable function, but risk is a multivariate function. According to the theory proposed, which we call the unified theory of risk, the riskiness of a proposition is a function of both the proportion and the modal closeness of the possible worlds at which the proposition holds. It is argued the theory passes the tests of extensional and formal adequacy.
Lymphadenopathy in systemic lupus erythematosus: no microbial trigger found by shotgun metagenomics in a retrospective study on 38 patients
Authors: Papo Matthias , Cappy Pierre , Degachi Alexandre , Woerther Paul-Louis , Saal Caroline , Charlotte Frédéric , Brocheriou Isabelle , Lhote Raphaël , Trefond Ludovic , Hié Miguel , Haroche Julien , Pha Micheline , Cohen-Aubart Fleur , Mathian Alexis , Rodriguez Christophe , Amoura Zahir 
Published: October 2024

Abstract

Objectives
Lymphadenopathy is a classical manifestation of SLE flare, occurring in approximately half of patients during the course of the disease. Lymphadenopathy in SLE is frequently associated with fever. Microbial infection may play a role in SLE onset and flares. The objectives of this study were to describe lymphadenopathy in the course of SLE and identify potential infectious triggers using microbial metagenomic analysis.

Methods
We performed a retrospective monocentric study of 38 patients with SLE who had lymph node biopsy at baseline or during follow-up. Shotgun metagenomics were performed in the patient’s lymph node biopsy to look for microbial RNA and/or DNA.

Results
Lymph node pathological analyses revealed follicular and/or paracortical hyperplasia in 73.7% of patients and histiocytic necrotizing lymphadenitis in 23.7%. At the time of biopsy, SLE patients exhibited fever in 29%, splenomegaly in 10%, cutaneous manifestations in 47%, polyarthritis in 32%, seritis in 13% and LN in 18%. Half of the patients (50%) had an increased CRP level, 35% had low C3, 65% had hypergammaglobulinemia. Microbial metagenomic analysis of lymph node biopsy revealed an absence of microbial DNA in 92% of patients, the presence of CMV in very small quantities in 2 patients, and the presence of HHV-7 in low quantities in a single patient.

Conclusion
Despite suggestion that certain microorganisms may play a role in the pathogenesis and flares of SLE, our microbial metagenomic analysis study did not highlight possible infectious triggering factors. Further and better-designed studies are needed to confirm these results.
High serum levels of CXCL13 predict lower response to csDMARDs in both ACPA-positive and ACPA-negative early rheumatoid arthritis
Authors: De Stefano Ludovico , Bozzalla Cassione Emanuele , Sammali Ylenia , Luvaro Terenzj , Montecucco Carlomaurizio , Manzo Antonio , Bugatti Serena 
Published: October 2024

Abstract

Objectives
Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with RA. Here we tested whether CXCL13 predicts response to first-line treatment with MTX in patients with early RA, independently and in association with ACPA and IgM-RF.

Methods
A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated. CXCL13, ACPA and IgM-RF were determined on baseline sera. Short-term variations of CXCL13 were measured after 2 months. The association of high CXCL13 (≥100 pg/ml) with disease remission after 6 months and escalation to second-line therapies within year 2 was evaluated in the total population and in ACPA subgroups separately.

Results
High levels of CXCL13 were found in 53.6% of ACPA-positive and 31.5% of ACPA-negative patients, with minimal association with disease activity and RF. Serum CXCL13 remained stable after 2 months. High baseline CXCL13 independently predicted failure to achieve remission and more frequent requirement of second-line treatment in ACPA-positive patients, with adjusted odds ratios (ORs) in the range of 0.17–0.49 for remission and 6.75 for second-line treatment. In ACPA-negative patients with high CXCL13, remission occurred at the expense of higher doses of MTX, and levels of CXCL13 predicted MTX escalations with an adjusted OR (95% CI) of 2.69 (1.35–5.34).

Conclusions
High serum levels of CXCL13 identify a subgroup of RA patients who are more refractory to first-line treatment with MTX. CXCL13 appears a promising biomarker of response to MTX in both ACPA-positive and -negative early RA.
Enhancing the in vivo bioavailability and absorption of Niclosamide with amorphous solid dispersion via solvent method
Authors: Li Jing , Chang Yu , Zou Zhiyang Zack 
Published: October 2024

Abstract

Objectives
This research aims to prepare a superior amorphous solid dispersion (ASD) formulation via solvent method for the oral delivery of Niclosamide to enhance oral bioavailability and absorption.

Methods
Phase solubility tests were conducted to select an optimal carrier combination for Niclosamide solid dispersion (SD). The Niclosamide ASD was synthesized using a solvent rotary evaporation method and characterized through in vitro dissolution tests, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction, and scanning electron microscopy. In vivo oral pharmacokinetic studies were conducted in Sprague Dawley rats at a dose of 50 mg/kg.

Key findings
PEG6000 and poloxamer 188 combination was selected as an optimal carrier. ASD named ASD-5 was successfully prepared, encompassing a 25% drug loading, Niclosamide within ASD-5 remains amorphous and stable. 75% of Niclosamide in ASD-5 rapidly dissolved in 5 min, while below 5% of pure Niclosamide and physical mixture dissolved in a longer time. Amorphization of Niclosamide in ASD-5 notably contributes to its dissolution rate and extent. Furthermore, among reported Niclosamide SD formulations with drug loading above 25%, ASD-5 demonstrated the highest bioavailability, showing a 2.33-fold increase in plasma exposure and bioavailability compared to pure Niclosamide.

Conclusions
Amorphous ASD-5 prepared by the solvent method has higher drug loading and is scalable in pre-clinical stage preparation. Due to using PEG6000 and poloxamer 188 combination, ASD-5 had the highest bioavailability among reported Niclosamide SDs with a drug load exceeding 25%. Also, ASD-5 presented a simplified preparation procedure compared to other reported Niclosamide SD.
The development of attitudes toward science and technology: a longitudinal analysis of Generation X
Authors: Miller Jon D , Laspra Belén , Polino Carmelo , Branch Glenn , Ackerman Mark S , Pennock Robert T 
Published: October 2024

Abstract
Research on public attitudes toward science and technology policy has relied on surveys taken at single points in time. These surveys fail to indicate how these attitudes develop or change. In this study, we use data from the Longitudinal Study of American Life that has followed a national sample of Generation X for 33 years—from middle school to midlife. We demonstrate that the critical period for the formation of attitudes toward science and technology is the 15–18 years after high school—college, work, family, and career. The attitudes formed in this period remain stable for most individuals during midlife. This work provides an important perspective for scientists, engineers, and the leadership of the scientific community in their efforts to foster positive attitudes toward science and technology and to understand the roots of concerns and reservations about science.
Isolation and characterisation of novel lytic bacteriophages for therapeutic applications in biofilm-associated prosthetic joint infections
Authors: Burton Nathan J , Melo Luís D R , Tadesse Michaël F D , Pearce Bethany , Vryonis Evangelos , Sagona Antonia P 
Published: October 2024

Abstract
Prosthetic joint infections are devastating complications of joint arthroplasties. Without effective management, they can lead to limb amputation and even death. A significant proportion of these infections is caused by the primarily commensal Coagulase-negative Staphylococci pathogens, which form thick, antibiotic-resistant biofilms at the site of infection. Combinatorial therapy involving antibiotics and bacteriophages may represent a strategy to overcome resistance. Previous research indicates that as bacteria develop resistance to antibiotics, they often become more susceptible to bacteriophages. In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.
Effects of Buprenorphine, Methadone, and Substance-Use on COVID-19 Morbidity and Mortality
Authors: Christian Nicholaus J. , Zhou Xin , Radhakrishnan Rajiv 
Published: October 2024

Objectives
Substance use disorder has been associated with increased morbidity in COVID-19 infection. However, less is known about the impact of active substance use and medications for opioid use disorder (MOUD) on COVID-19 outcomes. We conducted a retrospective cohort study to evaluate the impact of substance use, namely, cannabis, cocaine, alcohol, sedative and opioid use; and buprenorphine or methadone on COVID-19 morbidity and mortality.

Methods
Using electronic health record data at a large urban hospital system, patients who tested positive for COVID-19 between January 1, 2020, and December 31, 2021, were included. Substance use was identified from urine toxicology and MOUD prescriptions within 90 days prior to admission. COVID-19 outcomes included mortality, ICU admission, need for intubation, and number and duration of hospitalizations. Multivariable logistic regression was performed controlling for variables such as age, sex, medical comorbidity, tobacco use, and social disadvantage.

Results
Among COVID-19–positive patients (n = 17,423), sedative, cannabis, cocaine, and opioid use was associated with statistically significant increases in need for ICU care, need for ventilatory support, number of hospitalizations, and duration of hospitalization. Substance use was not associated with an increase in all-cause mortality. There were no statistically significant differences between methadone, buprenorphine, and other opioids on COVID-19 outcomes.

Conclusions
Active substance use was associated with increased morbidity in COVID-19 infection. MOUD was not associated with worse COVID-19 outcomes compared to other opioids. Future studies focused on MOUD treatments that reduce morbidity may help improve clinical outcomes in COVID-19.
A Qualitative Assessment of Adolescent Symptom Report and Caregiver Concordance Following Outpatient Surgery
Authors: Brown Sydney E.S. , Costa Camila , Kelly Alyssa , Oh Sarah , Waitzman Gillian , Dinh Dan , Clauw Daniel , Waljee Jennifer F. , Carlozzi Noelle E. 
Published: October 2024

Objectives:
Limited data exist regarding recovery from surgery from the adolescent’s perspective, or data regarding concordance between adolescent and caregiver symptom reports preventing appreciation of adolescent needs and hindering the provision of appropriate care.

Methods:
We conducted semi-structured interviews with adolescents ages 12 to 17 and a parent caregiver 2 weeks following a variety of outpatient elective surgeries about recovery symptoms. We used latent manifest content analysis to analyze interview data. Caregiver-adolescent response concordance was assessed using Cohen κ.

Results:
Interviews were conducted with 31 adolescent-caregiver pairs (median age: 15 y). Fifty-eight percent of adolescents and 84% of caregivers were female; 71% of adolescents were White. Twenty-three percent of children reported severe pain, some of which was not expected given the surgery. Severe pain was associated with nausea (71%, P=0.002), pain-related sleep disturbance (86%, P=0.007), and severe anxiety (43%, P=0.008). Fatigue was also common (58%), but not associated with severe pain (P=0.484) or sleep disturbance (P=0.577). Thirty-nine percent reported anxiety; 32% experienced anger/frustration. Caregiver-adolescent concordance was only substantial for severe pain (κ=0.71) and anger/frustration (κ=0.67). Caregiver reports also often included psychological symptoms not reported by their children, with qualitative evidence supporting caregiver accuracy.

Discussion:
Adolescents may experience significant physical symptoms, such as pain and fatigue, even after minor surgeries. Fatigue symptoms may be unrelated to pain or sleep. Caregiver report of adolescent psychological symptoms may be necessary to gain a complete understanding of those symptoms in this population.
The Kinetic and Kinematic Efficacy of Posterior Leaf Spring Ankle-foot Orthosis in Patients with Drop foot
Authors: Rahbar Soulmaz , Pourhoseingholi Ensieh , Hoseini Parinaz , Asgharian Seyedeh Fatemeh , Nouri Mohamad Javad , Mohamadi Somayeh , Piri Mohamed Mahdi 
Published: October 2024

Background:
Dorsi flexor weakness is one of the common consequences of stroke with a negative impact on normal walking. Posterior leaf spring (PLS) Ankle Foot Orthosis (AFO) is the most frequent prescription to assist foot clearance and leg propulsion in these patients. However, the real efficacy of this AFO needs more attention. This study aimed to investigate the efficacy of PLS AFO on gait outcomes as the most common AFO in drop foot post-stroke patients.

Methods:
The study design was a pre–post-test experiments in which twenty drop foot patients with a mean age of 65 years with a mean age of 58.45 (±5.23) years who were 4/5 years post-stroke. They walked at self-selected walking speed on a 10 meters walk away in two conditions of with their own shoes and PLS AFO. The 3D motion capture gait analysis system including 6 vicon cameras and a Kistler force plate were used in order to measure gait kinetic and kinematic variables. For each trial, each joints (ankle, knee and hip) angle, moment and power were averaged over one-minute walking.

Results:
Walking with PLS showed a statistically significant improve kinetic and kinematic variables in hip, knee and ankle joints included power, moments and angles at entire gait cycle. P<0.05.

Conclusions:
In our study of stroke patients who were fitted with a PLS AFO, immediate significant improvements occurred in most kinetic and kinematic than shoes only in sacrifice some others.
Inclusion body myositis: an update
Authors: Anderson Nicolaas C. , Lloyd Thomas E. 
Published: October 2024

Purpose of review
To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM).

Recent findings
Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy.

Summary
Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.
Releasing our model T – chimeric antigen receptor (CAR) T-cells for autoimmune indications
Authors: Wobma Holly , Chang Joyce C. , Prockop Susan E. 
Published: October 2024

Purpose of review
This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells.

Recent findings
To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1–2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response.

Summary
Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.