bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-natal and early life lead exposure and childhood inhibitory control: an item response theory approach to improve measurement precision of inhibitory control
Authors: Liu Shelley H. , Chen Yitong , Bellinger David , de Water Erik , Horton Megan , Téllez-Rojo Martha M. , Wright Robert 
Published: September 2024

Abstract
Background
Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure.

Methods
Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately.

Results
Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8–10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models.

Conclusion
This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data.
Universal screening of colorectal tumors for lynch syndrome: a survey of patient experiences and opinions
Authors: Petterson Alexander T. , Garbarini Jennifer , Baker Maria J. 
Published: September 2024

Abstract
Background
Lynch syndrome represents the most common hereditary cause of both colorectal and endometrial cancer. It is caused by defects in mismatch repair genes, as well as EPCAM. Universal screening of colon tumors for Lynch syndrome via microsatellite instability (MSI) and/or immunohistochemistry (IHC) can identify patients and families at risk to develop further cancers and potentially impact surveillance and treatment options. The approach to implementation of universal screening, taking ethical considerations into account, is critical to its effectiveness, with patient perspectives providing valuable insight.

Methods
Patients whose colon tumors underwent universal screening at Penn State Hershey Medical Center over a period of 2.5 years were mailed a survey on universal screening in 2017. Along with the survey, they received a recruitment letter and a summary explanation of research. The survey included both multiple choice and free-response questions that covered topics including respondent knowledge of Lynch syndrome, attitudes toward universal screening and experiences with the screening protocol as implemented.

Results
Sixty-six of 297 possible patients (22.2%) responded to the survey, including 13 whose screening results raised concern for Lynch syndrome. 75.8% of respondents supported universal tumor screening without informed consent. 92.4% preferred receiving screening results regardless of outcome. Respondents described benefits to screening for themselves and their families.

Conclusions
While broadly supporting universal tumor screening without informed consent, respondents also wanted more information shared about the screening policy, as well as their results. These patient preferences should be one of many factors considered when implementing universal screening and can also inform practices regarding both tumor profiling and universal genetic testing, which is becoming more prevalent.
Morphological description and genetic analysis of a new black fly species (Diptera: Simuliidae) in the subgenus Asiosimulium from central Thailand
Authors: Srisuka Wichai , Takaoka Hiroyuki , Taai Kritsana , Maleewong Wanchai , Aupalee Kittipat , Saeung Atiporn 
Published: September 2024

Abstract
Background
Black flies are among the most medically and veterinary important insects, as adult females of certain species are the sole vector of Onchocerca volvulus. Here, a new black fly species belonging to the subgenus Asiosimulium Takaoka & Choochote, 2005, is described and formally named as Simulium (Asiosimulium) kittipati sp. nov.

Methods
Pupae and larvae of black flies were collected from available substrates in the stream from central Thailand. Pupae were individually separated in plastic tubes and maintained until adult flies emerged. The emerged adult flies associated with their pupal exuviae and cocoon as well as mature larvae preserved in 85% ethanol were used to describe the new species based on an integrated approach of morphological examination and molecular analysis of the COI gene.

Results
The new species is characterized in the female by the medium-long sensory vesicle with a medium-sized opening apically, scutum with three faint longitudinal vittae, and the ellipsoidal spermatheca; in the male by the number of upper-eye (large) facets in 20 vertical columns and 21 horizontal rows, hind basitarsus slender, nearly parallel-sided, and median sclerite much wider and upturned apically; in the pupa by the head and thoracic integument densely covered with tiny tubercles, and the pupal gill of arborescent type with 28–30 filaments; and in the larva by the postgenal cleft deep, nearly reaching the posterior margin of the hypostoma, and dark pigmented sheath of the subesophageal ganglion. The DNA barcode successfully differentiated the new species from its congeners with an interspecific genetic divergence of 1.74–18.72%, confirming the morphological identification that the species is a new member of the subgenus Asiosimulium. Phylogenetic analyses also indicated that the new species is genetically closely related to Simulium phurueaense Tangkawanit, Wongpakam & Pramual, 2018, further supporting its morphological classification.

Conclusions
This is the ninth species assigned to the subgenus Asiosimulium within the genus Simulium Latreille, 1802. Taxonomic notes and identification keys are given to distinguish this new species from the eight known species members in its same subgenus. Additionally, a distribution map of all species members in this subgenus occurring in Thailand and other countries is provided.

Graphical abstract
A novel PDHK inhibitor restored cognitive dysfunction and limited neurodegeneration without affecting amyloid pathology in 5xFAD mouse, a model of Alzheimer’s disease
Authors: Sakimura Katsuya , Kawai Takashi , Nashida Reiko , Ishida Yuji , Harada Kana , Suzuki Takashi , Okuma Chihiro , Cole Gregory M. 
Published: September 2024

Abstract
Background
Alzheimer’s disease (AD) is the most common form of dementia. Although drugs focusing on reducing amyloid β slow progression, they fail to improve cognitive function. Deficits in glucose metabolism are reflected in FDG-PET and parallel the neurodegeneration and synaptic marker loss closely preceding cognitive decline, but the role of metabolic deficits as a cause or consequence of neurodegeneration is unclear. Pyruvate dehydrogenase (PDH) is lost in AD and an important enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle by converting pyruvate into acetyl-CoA. It is negatively regulated by pyruvate dehydrogenase kinase (PDHK) through phosphorylation.

Methods
In the present study, we assessed the in vitro/ in vivo pharmacological profile of the novel PDHK inhibitor that we discovered, Compound A. We also assessed the effects of Compound A on AD-related phenotypes including neuron loss and cognitive impairment using 5xFAD model mice.

Results
Compound A inhibited human PDHK1, 2 and 3 but had no inhibitory activity on PDHK4. In primary neurons, Compound A enhanced pyruvate and lactate utilization, but did not change glucose levels. In contrast, in primary astrocytes, Compound A enhanced pyruvate and glucose utilization and enhanced lactate production. In an efficacy study using 5xFAD mice, Compound A ameliorated the cognitive dysfunction in the novel object recognition test and Morris water maze. Moreover, Compound A prevented neuron loss in the hippocampus and cerebral cortex of 5xFAD without affecting amyloid β deposits.

Conclusions
These results suggest ameliorating metabolic deficits by activating PDH by Compound A can limit neurodegeneration and is a promising therapeutic strategy for treating AD.
The water–energy–food–ecosystem nexus in North Africa dryland farming: a multi-criteria analysis of climate-resilient innovations in Morocco
Authors: Kertolli Emirjona , Prosperi Paolo , Harbouze Rachid , Moussadek Rachid , Echchgadda Ghizlane , Belhouchette Hatem 
Published: September 2024

AbstractSmallholder farmers, who mostly engage in low-value agriculture in the drylands of Northern Africa, were the first to have felt the effects of climate change, with threats to their livelihoods and food security. The increasing costs of agricultural production, poor water and energy infrastructure, loss of agricultural land due to urban expansion, fragmented resource management, and unsustainable management practices all contribute to this vulnerability to climate change. This highlights the urgent need for innovative practices in farming systems. Within the framework of the water–energy–food–ecosystem nexus, this paper explores innovative practices in dryland farming systems, by assessing their impact on water, energy, food, and ecosystem through stakeholder perception. In this work, we aim to present a systems approach for assessing the resilience of the water–energy–food–ecosystem nexus in arid and semiarid regions. By using a multi-criteria analysis (MCA) approach, the study—which focuses on the Fès–Meknès region in Morocco—involves local actors to help researchers identify the key variables in order to assist farmers in their adaptation to climate change. The findings revealed different priorities between farmers and other stakeholders regarding the adoption of agricultural innovations. Farmers prioritize innovations that guarantee higher profitability and more market opportunities, such as integrating olive trees with cereal crops, by highlighting the importance of sustainable income sources. Meanwhile, stakeholders, such as researchers, engineers, government officials, and agribusiness entrepreneurs, prioritize innovations that emphasize high water use efficiency, which is crucial for the resilience of dryland farming areas: for instance, rainwater harvesting or the use of drought-resistant crop varieties that directly address the need for water conservation. But in doing so they are overlooking broader aspects within the water–energy–food–ecosystem nexus.
A rare case report of urogenital anomaly in a teenage girl: Herlyn–Werner–Wunderlich syndrome/OHVIRA syndrome (Obstructed Hemivagina and Ipsilateral Renal Anomaly)
Authors: Joel Govardhana Das , Basetti Bhavya , Mallula Balaji Varaprasad 
Published: September 2024

Abstract
Background
Herlyn–Werner–Wunderlich syndrome also known as OHVIRA syndrome is a rare complex congenital developmental anomaly characterized by the triad of uterine didelphys, obstructed hemivagina causing hematometrocolpos and ipsilateral renal anomaly.

Case presentation
Here we report a case of a 14-year-old girl who presented with acute onset lower abdominal pain. Ultrasound and magnetic resonance imaging showed uterus didelphys, hematometrocolpos, obstructed hemivagina and right renal agenesis. Patient underwent hematocolpos drainage.

Conclusions
OHVIRA syndrome is an uncommon congenital anomaly. Imaging plays a major role in diagnosis. Surgery is the treatment of choice to resect the septum and relieve the obstruction. An early correct diagnosis is the goal to relieve the symptoms and prevent complications, caused by retrograde menstruation which may result in endometriosis and, also, preserve sexual and conception abilities.
Spinal arachnoid web: a systematic review of a rare entity, with two illustrative case reports
Authors: Naggar Amine , El Ouali Ibtissam , Aidi Saadia , Melhaoui Adyl , Ech-cherif el Kettani Najwa , Fikri Meriem , Jiddane Mohamed , Touarsa Firdaous 
Published: September 2024

Abstract
Background
Spinal arachnoid web (AW) is a very rare entity, with a limited number of cases documented in the literature. Our manuscript represented a comprehensive general review, encompassing various aspects of the subject matter without focusing on any single element. The objective of this systematic review was to describe and analyze reported cases of surgically proven spinal arachnoid webs (AWs) to elucidate their imaging and clinical features, pathophysiology, and optimal management strategies, and to determine the total number of documented cases in the literature. Patterns and commonalities across reported cases were identified to provide a clearer framework for diagnosing and treating this elusive condition. A search of Web of Science, PubMed, and Scopus, respecting PRISMA guidelines, was conducted to include reported cases of surgically proven spinal AW. Our surgically proven case was included as well.

Main body of the abstract
The search yielded 196 cases of surgically confirmed spinal AWs in the literature. Adding our case, the total is 197. They are seen commonly in middle-aged patients, slightly more prevalent in males, and often without an evident cause. Sensation disturbances were the most frequently found clinical signs, followed by gait difficulties, weakness, and pain. Symptoms were predominantly located in the lower limbs and trunk. On imaging, an indentation to the rear aspect of the spinal cord was most frequently found at the mid-thorax followed by the upper thorax, often associated with a syrinx or a hyperintense T2 cord signal, usually extending rostrally. Excision was the most efficient treatment.

Short conclusion
The assessment found that AW cases are rare in the literature, indicating the disease's scarcity. It manifests insidiously, with the shortest latency reported being 2 weeks. Upper limb symptoms occur in a quarter of cases regardless of the AW's thoracic location, likely due to rostral syrinx and cerebrospinal fluid flow disturbances. Most pathology results revealed fibrous connective tissue, similar to findings in arachnoid cysts, suggesting that AW may result from a ruptured arachnoid cyst or its precursor. Using 3D SPACE STIR and CISS MRI sequences is recommended to visualize the arachnoid band directly.
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for
PIK3CA
-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Accordino Melissa K. , Bedard Philippe L. , Cervantes Andrés , Gambardella Valentina , Hamilton Erika , Italiano Antoine , Kalinsky Kevin , Krop Ian E. , Oliveira Mafalda , Schmid Peter , Saura Cristina , Turner Nicholas C. , Varga Andrea , Cheeti Sravanthi , Hilz Stephanie , Hutchinson Katherine E. , Jin Yanling , Royer-Joo Stephanie , Peters Ubong , Shankar Noopur , Schutzman Jennifer L. , Juric Dejan 
Published: September 2024

PURPOSE

To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with
PIK3CA
-mutated, hormone receptor–positive/human epidermal growth factor receptor 2–negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier:
NCT03006172
).

METHODS
Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability.

RESULTS
Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug–drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response.

CONCLUSION
Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.
Effects of Atrial Fibrillation Screening According to Thyroid Function: Post Hoc Analysis of the Randomized LOOP Study
Authors: Spona Daniel Camillo , Frodi Diana My , Xing Lucas Yixi , Kongebro Emilie Katrine , Haugan Ketil Jørgen , Graff Claus , Højberg Søren , Krieger Derk , Brandes Axel , Køber Lars , Olesen Morten S , Andersen Andreas , Hædersdal Sofie , Frikke-Schmidt Ruth , Svendsen Jesper Hastrup , Diederichsen Søren Zöga 
Published: September 2024

Abstract

Context
Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk.

Objective
This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels.

Methods
An AF screening trial (the LOOP study) was analyzed post hoc according to baseline TSH. The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included major bleeding, all-cause death, and the combination of stroke, SE, and cardiovascular death.

Results
TSH measurements were available in 6003 of 6004 trial participants, 1500 randomized to implantable loop recorder (ILR) screening for AF and anticoagulation upon detection vs 4503 to usual care; mean age was 74.7 ± 4.1 years and 2836 (47%) were women. AF detection was approximately triple for ILR vs usual care across TSH tertiles (adjusted P interaction = 0.44). In the first tertile, screening was associated with decreased risk of the primary outcome (hazard ratio [HR] 0.52, 95% CI 0.30-0.90; P = .02) and stroke, SE, or cardiovascular death (HR 0.54, 95% CI 0.34-0.84; P = .006) compared with usual care, while no effect was observed among participants with higher TSH (adjusted P interaction .03 and .01, respectively). There was no effect on other outcomes. Analyses of continuous TSH or excluding those with abnormal TSH or thyroid medication showed similar results.

Conclusion
AF screening and subsequent treatment was associated with decreased stroke risk among participants with low TSH, though the yield of screening was similar across TSH levels. TSH may be useful as a marker to indicate benefit from AF screening vs overdiagnosis and overtreatment. These findings should be considered exploratory and warrant further study.
Impaired 11β-HSD1 Activity in a Male Patient With Cushing Disease Resulting in Lack of the Full Cushingoid Phenotype
Authors: Weber Robert J , Kawaja Christopher , Wallerstein Robert , Kunwar Sandeep M , Liu Chienying 
Published: September 2024

Abstract
We present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. There have only been 2 prior reports of impaired 11β-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11β-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11β-HSD1 should be considered in the differential diagnosis.
Diagnosing Primary Hyperparathyroidism in Pregnancy: A Case of Altered Parathyroid Hormone Degradation in Pregnancy
Authors: Luong Dianna , Hawke Kate , De Waal Elzahn , Duke Madeline , Wolski Penny 
Published: September 2024

Abstract
Diagnosing primary hyperparathyroidism in pregnancy is difficult due to pregnancy-related changes in parathyroid hormone (PTH); calcium; 1,25 vitamin D; and renal calcium excretion. Parathyroid hormone–related peptide (PTHrP) produced by the placenta adds additional complexity. Our case is the first to demonstrate an increased rate of PTH degradation within a pregnant individual who returned unexpectedly low PTH levels. We describe a 27-year-old female patient who presented at 25 weeks gestation with pancreatitis and hypercalcemia. Primary hyperparathyroidism was suspected but variable PTH results led to uncertainty and an assay error was considered. PTH samples were collected in both serum-separating tubes (SST) and EDTA tubes and compared to controls (5 nonpregnant and 5 pregnant individuals). Samples were retested every 2 hours for a period of 10 hours. A rapid decline in the measured PTH was noted in the index case, an observation which differed from controls. We postulated that internal and/or external factors influenced the PTH measurement obtained from our patient. From our observations, rapid PTH degradation in pregnancy, and individual variation in PTH stability and laboratory processes, can influence PTH results and impact on interpreting hypercalcemia in pregnancy.