bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering acclimation to sublethal combined and sequential abiotic stresses in Arabidopsis thaliana
Authors: Jiang Zhang , Verhoeven Ava , Li Yihong , Geertsma Romy , Sasidharan Rashmi , van Zanten Martijn 
Published: October 2024

Abstract
Plants are frequently exposed to environmental challenges. Responses to sublethal abiotic stress combinations are complex and often distinct from responses to individual stresses and remain poorly understood. Investigating traits and molecular factors mediating acclimation to stress combinations is essential for the development of climate change-resilient field crops. Here, we studied the morphological, physiological, and molecular responses of Arabidopsis thaliana to (i) co-occurring high temperature and drought and (ii) flooding followed by drought, both of which have increased in frequency due to climate change, and the individual component stresses: high temperature, drought, and flooding. A set of 15 physiological and morphological traits were assessed during single and combined stresses. By combining these comprehensive trait analyses with transcriptome characterization, we detected generally additive negative effects of simultaneous or sequential stresses on plant morphology and physiology compared with the corresponding individual stresses. Although drought had a mild effect on various growth, morphological, and physiological traits in both stress combinations, a unique transcriptome signature emerged upon combination with high temperature simultaneously, or flooding sequentially. Molecular processes identified as important for multistress resilience included plastid–nucleus communication, abscisic acid signaling, and photo-acclimation. Based on the RNA-seq data, a set of 39 genes were identified as potential multistress response regulators. Mutants were tested to validate the contribution of these genes to plant survival and phenotypic acclimation under combined stress. We confirmed the involvement of several genes. Among the identified factors were EARLY FLOWERING 6 (ELF6) and ARABIDOPSIS TÓXICOS EN LEVADURA 80 (ATL80), with substantial effects on plant growth, leaf development, and plant survival (wilting) during high-temperature drought and postsubmergence drought, respectively.
Internet-based surveillance to track trends in seasonal allergies across the United States
Authors: Stallard-Olivera Elias , Fierer Noah 
Published: October 2024

Abstract
Over a quarter of adults in the United States suffer from seasonal allergies, yet the broader spatiotemporal patterns in seasonal allergy trends remain poorly resolved. This knowledge gap persists due to difficulties in quantifying allergies as symptoms are seldom severe enough to warrant hospital visits. We show that we can use machine learning to extract relevant data from Twitter posts and Google searches to examine population-level trends in seasonal allergies at high spatial and temporal resolution, validating the approach against hospital record data obtained from selected counties in California, United States. After showing that internet-derived data can be used as a proxy for aeroallergen exposures, we demonstrate the utility of our approach by mapping seasonal allergy-related online activity across the 144 most populous US counties at daily time steps over an 8-year period, highlighting the spatial and temporal dynamics in allergy trends across the continental United States.
Scleroderma renal crisis, an increasingly rare but persistently challenging condition: a retrospective cohort study
Authors: Shah Rushab C , Morrisroe Kathleen , Stevens Wendy , Ferdowsi Nava , Proudman Susanna , Nikpour Mandana , Ross Laura J 
Published: October 2024

Abstract

Objective
Scleroderma renal crisis (SRC) is associated with high morbidity and mortality and there remain unmet needs regarding early identification and treatment. We aimed to assess risk factors for and the outcomes of SRC at a large Australian tertiary hospital.

Methods
Seventeen incident SRC cases were diagnosed between 2012 and 2022. Demographic, SSc manifestations and treatment data were extracted. Using data from the Australian Scleroderma Cohort Study (n = 483), logistic regression analysis was performed to identify risk factors for SRC.

Results
The prevalence of SRC was 3.52%. The median SSc disease duration at SRC onset was 2 years [interquartile range (IQR) 1–4]. Peak creatinine occurred at a median of 11 days (IQR 5–14) post-SRC diagnosis, with a median peak creatinine of 144 µmol/l (IQR 86–306). Nine (52.94%) SRC patients had evidence of acute neurologic and/or cardiac complications. Acute haemofiltration was required in 3 (17.65%) patients. Over the follow-up period, 7 (41.18%) SRC patients died 2.75 years (IQR 0.74–7.25) after SRC onset. Patients with SRC were more likely to be male [odds ratio (OR) 9.73 (95% CI 3.57, 26.56)], have diffuse disease [OR 23.16 (95% CI 5.22, 102.80)] and have antibodies to Scl70 [OR 3.34 (95% CI 1.24, 9.04)] or RNA polymerase III (RNAPIII) [OR 5.15 (95% CI 1.91, 13.89)].

Conclusion
SRC is an uncommon manifestation, but outcomes remain poor. A significant proportion of patients presenting with SRC in Australia are positive for Scl70 or RNAPIII antibody. Despite relatively low peak serum creatinine and rates of renal replacement therapy, SRC was still associated with significant mortality.
Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study
Authors: Praastrup Fie J , de Thurah Annette , Hauge Ellen M , Rasmussen Linda A , Næser Esben U 
Published: October 2024

Abstract

Objectives
Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc.

Methods
We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between 1 January 2005 and 31 December 2018 were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references.

Results
A total of 1650 SSc patients (1255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48–68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen = 1.43 [95% CI: 1.33; 1.53], IRRmen = 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen = 1.86 [95% CI: 1.62; 2.14], IRRmen = 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen = 2.30 [95% CI: 2.16; 2.44], IRRmen = 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen = 5.62 [95% CI: 5.08; 6.20], IRRmen = 9.53 [95% CI: 7.81; 11.63]).

Conclusion
The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.
Development and intra-renal delivery of renal progenitor organoids for effective integration in vivo
Authors: Lim Diana , Kim Ickhee , Song Qianqian , Kim Ji Hyun , Atala Anthony , Jackson John D , Yoo James J 
Published: October 2024

Abstract
Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.
Complex Hybridization in a Clade of Polytypic Salamanders (Plethodontidae: Desmognathus) Uncovered by Estimating Higher-Level Phylogenetic Networks
Authors: Pyron R Alexander , O’Connell Kyle A , Myers Edward A , Beamer David A , Baños Hector 
Published: October 2024

Abstract
Reticulation between radiating lineages is a common feature of diversification. We examine these phenomena in the Pisgah clade of Desmognathus salamanders from the southern Appalachian Mountains of the eastern United States. The group contains 4–7 species exhibiting 2 discrete phenotypes, aquatic “shovel-nosed” and semi-aquatic “black-bellied” forms. These ecomorphologies are ancient and have apparently been transmitted repeatedly between lineages through introgression. Geographically proximate populations of both phenotypes exhibit admixture, and at least 2 black-bellied lineages have been produced via reticulations between shovel-nosed parentals, suggesting potential hybrid speciation dynamics. However, computational constraints currently limit our ability to reconstruct network radiations from gene-tree data. Available methods are limited to level-1 networks wherein reticulations do not share edges, and higher-level networks may be non-identifiable in many cases. We present a heuristic approach to recover information from higher-level networks across a range of potentially identifiable empirical scenarios, supported by theory and simulation. When extrinsic information indicates the location and direction of reticulations, our method can successfully estimate a reduced possible set of nonlevel-1 networks. Phylogenomic data support a single backbone topology with up to 5 overlapping hybrid edges in the Pisgah clade. These results suggest an unusual mechanism of ecomorphological hybrid speciation, wherein a binary threshold trait causes some hybrid populations to shift between microhabitat niches, promoting ecological divergence between sympatric hybrids and parentals. This contrasts with other well-known systems in which hybrids exhibit intermediate, novel, or transgressive phenotypes. The genetic basis of these phenotypes is unclear and further data are needed to clarify the evolutionary basis of morphological changes with ecological consequences.
Misadventures and traps in stamp duty dodging in Singapore
Authors: Ooi Vincent 
Published: October 2024

Abstract
As stamp duty rates in Singapore have increased over time, so too have the number of stamp duty avoidance schemes, ranging from simple and straightforward to complex and elaborate. Even when these schemes technically succeed, any potential loopholes are quickly dealt with legislatively. But stamp duty avoidance attempts can also backfire with heavy resulting costs. Changes such as the stamp duty avoidance surcharge discourage aggressive planning. The most severe consequences occur when property buyers go beyond mere avoidance and enter the more dangerous territory like evasion. This article cautions against a range of missteps, each more serious than the last.
Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice
Authors: Zheng Hong-xing , Xu You-mei , Fan Shu-cong , Qi Shan-shan , Jia Fan-fan , Wu Wei , Chen Chen 
Published: October 2024

Abstract

Background
Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice.

Methods
Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase.

Results
The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels.

Conclusions
Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.
Leaving the Shadows Behind? Effects of Domestic Workers Reform on Mothers’ Formal Employment
Authors: Boruchowicz Cynthia 
Published: October 2024

Abstract
What happens when new labor regulations are implemented and enforced while a welfare cash transfer program is already in place? Argentinean National Law 26.844 of 2013 aimed to increase formalization rates in the domestic work sector by increasing access to benefits for workers and enforcement mechanisms for household employers. Compared to those with older children, a 5 percentage–point lower increase in formalization among domestic workers with children under 18 years of age (a key eligibility criterion for welfare) is found after the introduction of the regulation. Moreover, there is suggestive evidence that this may stem from domestic workers’ concerns about losing welfare payments, although it is unclear whether this fear arises from misunderstanding, lack of information, or distrust in the reform. These findings underscore the importance of policy designs that mitigate potential disincentives and ensure that they do not undermine efforts to increase formal sector participation.
BRASH syndrome
Authors: Williams Kaegan G. , Robeck Rachel S. 
Published: October 2024

ABSTRACT
Bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia (BRASH) can combine into a vicious cycle that can present as bradycardia refractory to the Advanced Cardiac Life Support bradycardia algorithm. Early identification and treatment of BRASH syndrome are paramount to prevent patient deterioration into multiorgan failure.
Alcohol, Tobacco, and Marijuana Use Among Individuals Receiving Prescription Opioids for Pain Management
Authors: Miller-Matero Lisa R. , Pappas Celeste , Altairi Samah , Sehgal Monica , Chrusciel Timothy , Salas Joanne , Secrest Scott , Wilson Lauren , Carpenter Ryan W. , Sullivan Mark D. , Ahmedani Brian K. , Lustman Patrick J. , Scherrer Jeffrey F. 
Published: October 2024

Objective:
Substance use among individuals receiving prescription opioids for pain may be associated with poorer functioning. The purpose of this study was to examine whether the use of substances (ie, alcohol, marijuana, or tobacco) among individuals prescribed opioids for pain management was associated with pain, psychiatric disorders, and opioid misuse.

Methods:
Patients with non-cancer pain and a new opioid prescription were recruited from 2 health systems. Participants (N = 827) completed measures regarding pain severity, pain interference, psychiatric symptoms, and substance use.

Results:
Substance use was common with 58.0%, 26.2%, and 28.9% reporting alcohol, tobacco, and marijuana use, respectively. The use of tobacco or marijuana was associated with poorer functioning. Those with tobacco use had greater pain severity, interference, number of pain sites, and concern for opioid misuse, and were more likely to have probable depression, anxiety, and posttraumatic stress disorders. Participants reporting marijuana use were more likely to have higher concerns for opioid misuse scores and probable depression, anxiety, and posttraumatic stress disorders. Use of alcohol was associated with lower pain severity and interference and fewer number of pain sites.

Conclusion:
Substance use is common among individuals receiving prescription opioids. Some types of substance use may be related to poorer opioid, pain, and psychiatric functioning. Clinicians prescribing opioids for pain management should assess for substance use, including tobacco, and be aware of the association with poorer functioning. Interventions could target pain, psychiatric symptoms, and substance use simultaneously to optimize outcomes for individuals with pain and substance use.
Pathogenesis of psoriatic arthritis: new insights from a bone marrow perspective
Authors: Saeed Fatima , Adamopoulos Iannis E. 
Published: October 2024

Purpose of review
Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases.

Recent findings
The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis.

Summary
These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.
Opportunistic Computed Tomography
Authors: Reid Jared , Tobin Jacqueline , McCrosson Matthew , Rivas Gabriella , Rothwell Stacey , Ravinsky Robert , Lawrence James 
Published: October 2024

Study Design:
Retrospective review.

Objective:
To use opportunistic computed tomography (CT) screening to determine the prevalence of osteoporosis (OP) in patients presenting with spinal fractures and the rate of identification and treatment at our institution.

Background:
OP remains a highly underdiagnosed and undertreated disease. Opportunistic abdominopelvic CT scans offer a feasible, accessible, and cost-effective screening tool for OP.

Methods:
Retrospective review of 519 patients presenting as trauma activation to the emergency department of a Level 1 Trauma Center after a spinal fracture. Patients were excluded if under the age of 18 or lacking a CT scan upon arrival in the emergency department. Hounsfield Units (HU) were measured at the L1 vertebral level on CT scans to determine bone density levels. Values of ≤100 HU were considered osteoporotic, whereas 101–150 HU were osteopenic.

Results:
A total of 424 patients were included. The average HU was 204.8 ± 74.3 HU. Of the patients, 16.7% were diagnosed as osteopenic and 9.9% as osteoporotic. The mean age was 65 ± 14 years for osteopenic patients and 77 ± 11 years for osteoporotic. A statistically significant inverse relationship was found between age and bone density. Of the patients, 42.5% with low bone density HU measurements had a previously documented history of OP/osteopenia. There was a statistically significant association between females and low bone density. Patients injured in a fall were statistically significantly more likely to have lower bone densities than those in motor vehicle accidents. Of the osteoporotic patients, 9.5% were treated by our institution’s fragility fracture team.

Conclusions:
Our study shows that among a cohort of patients with spinal fractures, 58% of patients with radiographic signs of OP are currently undiagnosed, resulting in a low treatment rate of OP. Increasing and standardizing the use of opportunistic CT scans would allow an increase in the diagnosis and treatment of OP in patients with spinal fractures. Further, opportunistic CT scans could also be useful for a broader orthopedic population at high risk of fragility fractures.

Level of Evidence:
Level II—therapeutic.
Influence of Right and Left Bundle Branch Block in Patients With Cardiogenic Shock and Cardiac Arrest
Authors: Rusnak Jonas , Schupp Tobias , Weidner Kathrin , Ruka Marinela , Egner-Walter Sascha , Forner Jan , Schmitt Alexander , Akin Muharrem , Tajti Péter , Mashayekhi Kambis , Ayoub Mohamed , Akin Ibrahim , Behnes Michael 
Published: October 2024

OBJECTIVES:
The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis.

DESIGN:
Prospective registry-study.

SETTING:
ICU of a tertiary academic hospital in Germany.

PATIENTS:
Adult patients with CS.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107–2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018–1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001–1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001–1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure.

CONCLUSIONS:
Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.