bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenomic description of a Mexican cohort with differences in sex development
Authors: Olivera-Bernal Grecia C. , De Ita-Ley Marlon , Ricárdez-Marcial Edgar F. , Garduño-Zarazúa Luz María , González-Cuevas Ángel Ricardo , Sepúlveda-Robles Omar A. , Huicochea-Montiel Juan Carlos , Cárdenas-Conejo Alan , Santana-Díaz Laura , Rosas-Vargas Haydeé 
Published: July 2024

Abstract
Background
Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500–5500, which can increase to 1:200–300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital.

Methods
Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City.

Results
One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification.

Conclusion
The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.
The overexpression of DSP1 in neurons induces neuronal dysfunction and neurodegeneration phenotypes in Drosophila
Authors: Baek Si-Eun , Kwon Younghwi , Yoon Jong-Won , Kim Hyo-Sung , Yang Jae-Yoon , Lee Dong-Seok , Yeom Eunbyul 
Published: July 2024

AbstractDorsal switch protein 1(DSP1), a mammalian homolog of HMGB1, is firstly identified as a dorsal co-repressor in 1994. DSP1 contains HMG-box domain and functions as a transcriptional regulator in Drosophila melanogaster. It plays a crucial role in embryonic development, particularly in dorsal–ventral patterning during early embryogenesis, through the regulation of gene expression. Moreover, DSP1 is implicated in various cellular processes, including cell fate determination and tissue differentiation, which are essential for embryonic development. While the function of DSP1 in embryonic development has been relatively well-studied, its role in the adult Drosophila brain remains less understood. In this study, we investigated the role of DSP1 in the brain by using neuronal-specific DSP1 overexpression flies. We observed that climbing ability and life span are decreased in DSP1-overexpressed flies. Furthermore, these flies demonstrated neuromuscular junction (NMJ) defect, reduced eye size and a decrease in tyrosine hydroxylase (TH)-positive neurons, indicating neuronal toxicity induced by DSP1 overexpression. Our data suggest that DSP1 overexpression leads to neuronal dysfunction and toxicity, positioning DSP1 as a potential therapeutic target for neurodegenerative diseases.
Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation
Authors: Leali Marco , Marongiu Ines , Spinelli Elena , Chiavieri Valentina , Perez Joaquin , Panigada Mauro , Grasselli Giacomo , Mauri Tommaso 
Published: July 2024

Abstract
Background
Assessment of regional ventilation/perfusion (V′/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V′/Q mismatch.

Methods
We enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V′/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V′/Q-ABS), left unadjusted (V′/Q-REL), or corrected by MV/CO ratio derived from EIT data (V′/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units ($${\text{V}}_{{\text{D}}}^{\prime }$$

V

D

′

/QSHUNT) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (QND/$${\text{V}}_{{{\text{DS}}}}^{\prime }$$

V

DS

′

) was calculated as an index of hypocapnic pneumoconstriction.

Results
Our calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V′/Q-ABS, V′/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V′/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V′/Q units. The heterogeneity of ventilation and perfusion reaching different V′/Q compartments was underestimated. V′/Q-CORR maps eliminated all these differences with V′/Q-ABS (p > 0.05). Higher $$V_{D}^{\prime } /Q_{SHUNT}$$

V

D

′

/

Q

SHUNT

correlated with higher PaO2/FiO2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ =  − 0.59, p = 0.005). Higher $$Q_{ND} /V_{DS}^{\prime }$$

Q

ND

/

V

DS

′

correlated with lower PEEP (ρ =  − 0.62, p = 0.003) and plateau pressure (ρ =  − 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively).

Conclusions
Regional V′/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.
New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation
Authors: Ayoup Mohammed Salah , Ghanem Mariam , Abdel-Hamid Hamida , Abu-Serie Marwa M. , Masoud Aliaa , Ghareeb Doaa A. , Hawsawi Mohammed B. , Sonousi Amr , Kassab Asmaa E. 
Published: July 2024

AbstractA series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives’ significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development.
Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats
Authors: Nikpendar Mahvash , Javanbakht Mohammad , Moosavian Hamidreza , Sajjadi Sepideh , Nilipour Yalda , Moosavian Toktam , Fazli Mahsa 
Published: July 2024

Abstract
Background
Episodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction.

Methods
Thirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term.

Results
The mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus.

Conclusion
Recurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions.
Doing a double take: when transthoracic echocardiography fails for mitral valve annuloplasty ring endocarditis with Streptococcus pyogenes: a case report
Authors: Schilling Jonathan K. , Tungate Robert , Patel Pranav M. , Sun Jack , Frangieh Antonio H. 
Published: July 2024

Abstract
Background
This case highlights several complications of a late and rare presentation of culture-negative Streptococcus pyogenes endocarditis of a previously repaired mitral valve with an annuloplasty ring including recurrent cardioembolic strokes, which was initially missed on transthoracic echocardiography.

Case presentation
A 66-year-old Caucasian female with prior mitral valve prolapse status post mitral valve annuloplasty and left atrial appendage occlusion, followed by two strokes, presented with supraventricular tachycardia that resolved spontaneously. During an inpatient admission, she developed symptoms of another stroke, and imaging studies were suggestive of recurrent cardioembolic phenomenon. Additional workup revealed two small intra-atrial masses adherent to the mitral annuloplasty ring missed on prior evaluation for recurrent stroke. She underwent surgical repair in the setting of a chronic culture-negative infectious endocarditis with Streptococcus pyogenes and recovered well with no further cardioembolic phenomenon.

Conclusion
This case serves to highlight the importance of having a higher index of suspicion in any cardiac prosthesis patient for endocarditis when presenting with symptoms such as recurrent stroke, arrhythmias, and abnormal cardiac lab work. It also demonstrates the need for appropriate imaging with transthoracic echocardiography followed by transesophageal echocardiography and reviews surgical indications to diagnose and treat culture-negative endocarditis.
Multiple lung abscesses and cold agglutinin syndrome following coronavirus disease 2019: a case report
Authors: Aga Masaharu , Okubo So , Ikeda Toshiki , Higashi Yuko , Hamakawa Yusuke , Matsuzaka Suguru , Miyazaki Kazuhito , Taniguchi Yuri , Misumi Yuki , Agemi Yoko , Nakamura Yukiko , Shimokawa Tsuneo , Aisa Yoshinobu , Okamoto Hiroaki 
Published: July 2024

Abstract
Background
Cold agglutination syndrome is a subtype of autoimmune hemolytic anemia. The condition is referred to as “cold” because the antibodies become active and induce hemolysis at cold temperatures, typically 3–4 °C, which is not always the case in other kinds of autoimmune hemolytic anemia. Whereas primary cold agglutination syndrome may occur in the absence of underlying conditions, secondary cold agglutination syndrome is associated with the presence of underlying infections, including coronavirus disease 2019.

Case presentation
We report the case of a 69-year-old Japanese woman with periodontitis who was referred to our hospital with complaints of brown-colored urine and chest pain. Her hemoglobin level was 6.1 g/dL. Computed tomography revealed multiple lung abscesses. Her direct antibody test results were positive (2+) for anti-complement direct antiglobulin and negative for immunoglobulin G, and her cold agglutinin titer was elevated at 1:4096. Workup for anemia revealed a positive result for cold agglutination syndrome. The patient had received the fourth dose of coronavirus disease 2019 vaccination. Nasopharyngeal swab test for detecting severe acute respiratory syndrome coronavirus 2 using a real-time reverse-transcription polymerase chain reaction gave a cycle threshold value of 42.3, and the level of virus-specific immunoglobulin G was elevated at 7.71 S/C (normal range −1.4 S/C).

Conclusion
A decrease in hemoglobin in patients with coronavirus disease 2019 may be associated with secondary cold agglutination syndrome. The patient was hypothesized to have developed multiple lung abscesses with secondary cold agglutination syndrome following coronavirus disease 2019. Thus, following coronavirus disease 2019, patients can develop secondary cold agglutination syndrome, which could worsen owing to associated bloodstream bacterial infections.
Sex differences in membrane properties and cellular excitability of dopamine D1 receptor-expressing neurons within the shell of the nucleus accumbens of pre- and mid-adolescent mice
Authors: Aziz Heather C. , Mangieri Regina A. 
Published: July 2024

Abstract
Background
The transition from childhood to adulthood, or adolescence, a developmental stage, is characterized by psychosocial and biological changes. The nucleus accumbens (NAc), a striatal brain region composed of the core (NAcC) and shell (NAcSh), has been linked to risk-taking behavior and implicated in reward seeking and evaluation. Most neurons in the NAc are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1R +) and/or dopamine D2 receptors (D2R +). Changes in dopaminergic and glutamatergic systems occur during adolescence and converge in the NAc. While there are previous investigations into sex differences in membrane excitability and synaptic glutamate transmission in both subdivisions of the NAc, to our knowledge, none have specified NAcSh D1R + MSNs from mice during pre- and mid-adolescence.

Methods
Sagittal brain slices containing the NAc were prepared from B6.Cg-Tg(Drd1a-tdTomato)6Calak/J mice of both sexes from postnatal days 21–25 and 35–47, representing pre- and mid-adolescence, respectively. Whole-cell electrophysiology recordings were collected from NAcSh D1R + MSNs in the form of membrane-voltage responses to current injections, to assess membrane properties and action potential waveform characteristics, and spontaneous excitatory postsynaptic currents (sEPSCs) to assess glutamatergic synaptic activity.

Results
Relative to pre-adolescent males, pre-adolescent female NAcSh D1R + MSNs exhibited a less hyperpolarized resting membrane potential, increased input resistance, and smaller action potential afterhyperpolarization amplitudes. During mid-adolescence, decreased input resistance and a shorter action potential duration in females were the only sex differences observed.

Conclusions
Taken together, our results indicate that NAcSh D1R + MSNs in mice exhibit sex differences in membrane properties and AP waveform during pre-adolescence that are overall indicative of increased cellular excitability in females and are suggestive of possible sex differences in glycine receptors, inwardly-rectifying potassium channels, and large conductance voltage-gated potassium channels. These differences do not appear to persist into mid-adolescence, when sex was observed to affect input resistance oppositely to that of pre-adolescence and AP waveform in a manner suggestive of differences in voltage-gated potassium channels.
Social costs associated with fibromyalgia in Spain
Authors: Oliva-Moreno J , Vilaplana-Prieto C 
Published: July 2024

Abstract
Background
Fibromyalgia is a chronic rheumatic disease of unknown aetiology, highly disabling and mainly affecting women. The aim of our work is to estimate, on a national scale, the economic impact of this disease on the employment of patients and non-professional (informal) care dimension.

Methods
Survey on Disabilities, Autonomy and Dependency carried out in Spain in 2020/21 was used to obtain information on disabled individuals with AD and their informal caregivers. Six estimation scenarios were defined as base case, depending on whether the maximum daily informal caregiving time was censored or not, and on the approach chosen for the valuation of informal caregiving time (contingent valuation and replacement time). Another six conservative scenarios were developed using the minimum wage for the estimation of labour losses.

Results
Our estimates range from 2,443.6 (willingness to pay, censored informal care time) to 7,164.8 million euros (replacement cost, uncensored informal care time) (base year 2021). Multivariate analyses identified that the degree of dependency of the person suffering from fibromyalgia is the main explanatory variable for both the probability of being employed and the time spent in informal care. Conservative scenarios estimates range from 1,807 to 6,528 million euros.

Conclusions
The high economic impact revealed should help to position a health problem that is relatively unknown in society and for which there are significant research and care gaps to be filled.
SUMOylation of nuclear receptor Nor1/NR4A3 coordinates microtubule cytoskeletal dynamics and stability in neuronal cells
Authors: Gagnon Jonathan , Caron Véronique , Tremblay André 
Published: July 2024

Abstract
Background
Nor1/NR4A3 is a member of the NR4A subfamily of nuclear receptors that play essential roles in regulating gene expression related to development, cell homeostasis and neurological functions. However, Nor1 is still considered an orphan receptor, as its natural ligand remains unclear for mediating transcriptional activation. Yet other activation signals may modulate Nor1 activity, although their precise role in the development and maintenance of the nervous system remains elusive.

Methods
We used transcriptional reporter assays, gene expression profiling, protein turnover measurement, and cell growth assays to assess the functional relevance of Nor1 and SUMO-defective variants in neuronal cells. SUMO1 and SUMO2 conjugation to Nor1 were assessed by immunoprecipitation. Tubulin stability was determined by acetylation and polymerization assays, and live-cell fluorescent microscopy.

Results
Here, we demonstrate that Nor1 undergoes SUMO1 conjugation at Lys-89 within a canonical ψKxE SUMOylation motif, contributing to the complex pattern of Nor1 SUMOylation, which also includes Lys-137. Disruption of Lys-89, thereby preventing SUMO1 conjugation, led to reduced Nor1 transcriptional competence and protein stability, as well as the downregulation of genes involved in cell growth and metabolism, such as ENO3, EN1, and CFLAR, and in microtubule cytoskeleton dynamics, including MAP2 and MAPT, which resulted in reduced survival of neuronal cells. Interestingly, Lys-89 SUMOylation was potentiated in response to nocodazole, a microtubule depolymerizing drug, although this was insufficient to rescue cells from microtubule disruption despite enhanced Nor1 gene expression. Instead, Lys-89 deSUMOylation reduced the expression of microtubule-severing genes like KATNA1, SPAST, and FIGN, and enhanced α-tubulin cellular levels, acetylation, and microfilament organization, promoting microtubule stability and resistance to nocodazole. These effects contrasted with Lys-137 SUMOylation, suggesting distinct regulatory mechanisms based on specific Nor1 input SUMOylation signals.

Conclusions
Our study provides novel insights into Nor1 transcriptional signaling competence and identifies a hierarchical mechanism whereby selective Nor1 SUMOylation may govern neuronal cytoskeleton network dynamics and resistance against microtubule disturbances, a condition strongly associated with neurodegenerative diseases.