bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease
Authors: Evenepoel Pieter , Jørgensen Hanne Skou 
Published: April 2024

Purpose of review
Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD.

Recent findings
Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness.

In summary
Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.
Characterizing autoimmune uveitis to systemic diseases: a retrospective study from a Syrian tertiary reference center
Authors: Kudsi Maysoun , Al-Darwish Lama , Khalayli Naram , Abouharb Dani , Abouharb Lana , Almajzoub Rahaf , Deeb Haya 
Published: April 2024

Background:
Uveitis, a notable cause of severe visual impairment, is frequently characterized as infectious or noninfectious autoimmune uveitis (AU), the latter of which is commonly associated with younger individuals and systemic diseases. Despite the condition’s widespread impact, there are substantial gaps in the comprehension of its pathogenesis, clinical presentation, and therapeutic response, particularly concerning systemic disease-associated uveitis.

Aim of the study:
The current study aims to bridge these gaps through an extensive examination of demographic and clinical features in AU patients, thereby informing future research, and therapeutic strategies, and improving patient outcomes.

Methods:
This retrospective observational study analyzed 261 patients with systemic disease-associated uveitis from January 2018 to December 2022 in Damascus, Syria. With diagnoses made using the Standardization of Uveitis Nomenclature Working Group Criteria, the study evaluated tailored treatment efficacy at the 24-month post-treatment mark, alongside comprehensive ophthalmic examinations, laboratory evaluations, and radiographic assessments.

Results:
In our study, included 87 patients with Systemic Disease-Associated Autoimmune Uveitis (SDA-AU). Women represented 64.36% of this group, and the mean age at diagnosis was 39.8±17.9 years (range 7–71) for men and 43.8±15.4 years (range 11–69). The most reported symptom was a painful red eye (52.87%). The onset of symptoms was sudden for 32.18% of patients, while 67.81% reported gradual development. Complications occurred in 33.33% of patients, including cataracts (41.37% of those with complications) and glaucoma (17.24%). Laboratory evaluations showed elevated inflammation markers in 66.66% of patients. Upon the 24-month assessment, 48.27% of patients achieved complete remission, 37.93% showed significant improvement, while disease worsened in 13.79% of cases.

Conclusion:
Our findings demonstrated that the presentation of AU in this cohort frequently precedes the diagnosis of systemic diseases, affirming the vital role of an early and accurate diagnosis of uveitis for the detection of underlying systemic conditions. In conclusion, our study underlines the significance of a comprehensive and multidisciplinary approach in the management of SD-AU, leading to improved prognosis and quality of life for patients.
Identification of important symptoms and diagnostic hypothyroidism patients using machine learning algorithms
Authors: Rakhshani Rad Salahuddin , Mohammadi Zahra H. , Zadeh Mahdieh J. , Mosleh-Shirazi Mohammad A. , Dehesh Tania 
Published: April 2024

Background:
Hypothyroidism is one of the most common endocrine diseases. It is, however, usually challenging for physicians to diagnose due to nonspecific symptoms. The usual procedure for diagnosis of Hypothyroidism is a blood test. In recent years, machine learning algorithms have proved to be powerful tools in medicine due to their diagnostic accuracy. In this study, the authors aim to predict and identify the most important symptoms of Hypothyroidism using machine learning algorithms.

Method:
In this cross-sectional, single-center study, 1296 individuals who visited an endocrinologist for the first time with symptoms of Hypothyroidism were studied, 676 of whom were identified as patients through thyroid-stimulating hormone testing. The outcome was binary (with Hypothyroidism /without Hypothyroidism). In a comparative analysis, random forest, decision tree, and logistic regression methods were used to diagnose primary Hypothyroidism.

Results:
Symptoms such as tiredness, unusual cold feeling, yellow skin (jaundice), cold hands and feet, numbness of hands, loss of appetite, and weight Hypothyroidism gain were recognized as the most important symptoms in identifying Hypothyroidism. Among the studied algorithms, random forest had the best performance in identifying these symptoms (accuracy=0.83, kappa=0.46, sensitivity=0.88, specificity=0.88).

Conclusions:
The findings suggest that machine learning methods can identify Hypothyroidism patients who show relatively simple symptoms with acceptable accuracy without the need for a blood test. Greater familiarity and utilization of such methods by physicians may, therefore, reduce the expense and stress burden of clinical testing.
Effects on ondansetron of postdural puncture headache after cesarean section under spinal anesthesia
Authors: Baharvand Forough , Vahabi Sepideh , Beiranvand Siavash 
Published: April 2024

Background:
Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an antiemetic for cancer treatment and analgesia-induced nausea and vomiting. In this study, the authors aim to evaluate the effect of postoperative ondansetron on PDPH.

Methods:
In this randomized controlled clinical trial study, 120 pregnant patients are ASA ll, undergoing elective cesarean section, were randomized into two groups (placebo or study). The patients in the study group, immediately after the birth of a baby and 24 h after the operation, received ondansetron 4 mg IV while the placebo group received a placebo. The severity and incidence of headache, postoperative nausea and vomiting, dizziness, neck and lower back pain, and the use of analgesia was assessed in the two groups.

Results:
The significant meaning of the time effect (P<0.001) indicated that regardless of the group, for each unit increase in time, the chance of developing a headache increased by 23%, which was statistically significant. Also, the significant meaning of the group effect indicated that regardless of time, patients who did not take indomethacin had ~4.11 times higher chances of developing a headache compared to those who received the medication, which was statistically significant (P=0.004).

Conclusion:
The administration of ondansetron significantly reduces the occurrence of postspinal anesthesia headaches and neck pain. There was no significant difference in headache severity between the two study groups.
What is the materno-fetal prognosis of adrenal insufficiency and pregnancy in low-resource setting? a case report
Authors: Soumana Diaouga Hamidou , Ziberou Assadick Oumar , Chaibou Yacouba Maimouna , Oumara Maina , Guédé Salamatou , Adamou Abdoulkader , Adehossi Eric O. , Mahamane Sani Mahamane A. , Nayama Madi 
Published: April 2024

Introduction and importance:
Adrenal insufficiency is a rare chronic disease with a prevalence of 39 to 60 cases per million peoples in Europe. However, the prevalence is higher in sub-saharian Africa. The occurrence of pregnancy in adrenal insufficiency is rare but associated with high maternal and perinatal morbidity and mortality. For this reason, the management of pregnancy in adrenal insufficiency patient must be provided by a multidisciplinary team.

Case presentation:
The authors report the case of a 34-year-old pregnant woman followed for adrenal insufficiency secondary to prolonged corticosteroid therapy. Treatment consisted to an obstetrical and endocrinological follow-up and corticosteroid replacement therapy with hydrocortisone. A prophylactic cesarean section at 38 weeks resulted in the birth of a newborn male weighing 3395 g. Maternal and perinatal prognosis was good.

Clinical discussion:
Pregnancy in adrenal insufficiency is a therepeutic challenge in developing countries. Through this case, the authors discuss the therapeutic and prognostic aspects of adrenal insufficiency in our setting.

Conclusion:
With the introduction of gluco-corticosteroid replacement therapy, pregnancy in adrenal insufficiency can progress normally.
Malignancy and “Violated Neck” Rates in Consecutive Cohort of 79 Adult Patients With Solitary Cystic Neck Mass—Lessons Learned and Recommendations for Clinical Practice Guidelines
Authors: Pupić-Bakrač Jure , Jayasekara Sandeep , Peiris Prasangi M. , Jayasinghe Liyanaarachchige A.H. , Kapugama Kanchana , Jayasuriya Nadeena S.S. , Wijekoon Parakrama , Attygalla Manjula 
Published: April 2024

Objective:
The neck region is a common site for solitary cystic neck mass (SCNM) of various etiologies, including congenital, inflammatory, and neoplastic. In adults, the primary focus is excluding malignancy. The objective of this study was to retrospectively analyze the accuracy of available diagnostic technologies for the differentiation of benign and malignant SCNM in adult patients. The study aimed to develop new clinical practice guidelines for evaluating and managing SCNM.

Methods:
The primary predictive variables were the diagnostic utilities of fine-needle aspiration cytology (FNAC), ultrasound (U/S), multislice computed tomography, and magnetic resonance imaging. The study’s endpoint was the overall diagnostic accuracy in differentiating between benign and malignant SCNM. The final diagnosis was based on histopathology.

Results:
The study included 79 adult patients: 55 (69.62%) male and 24 (30.38%) female (P<0.05). The mean age at presentation was 42.1 years (range: 18–84 years). Solitary cystic neck mass was distributed in the anterior neck region in 30 (37.97%) patients and the posterolateral neck regions in 49 (62.03%) patients (P<0.05). The posterolateral neck regions had a significantly higher rate of malignant SCNM than the anterior neck region [19/49 (38.78%) versus 1/30 (3.33%)] (P<0.05). There was no statistically significant difference between the U/S+FNAC and U/S+FNAC+multislice computed tomography and/or magnetic resonance imaging groups in differentiating benign and malignant SCNM (40/42 versus 36/37, P>0.05). “Violated neck” was recorded in 2 cases.

Conclusion:
A systematic investigation protocol should be applied to evaluate adult patients with SCNM.
Bisphenol A and its Analogues Alter Appetite Control in Zebrafish
Authors: Karim Silvia , Bondesson Maria 
Published: April 2024

AbstractThe regulation of appetite is of growing interest due to the significant rise in global obesity rates. Hunger and satiety are controlled by two hormones with functional activity in the brain; leptin, which is produced in adipocytes and suppresses food intake, and ghrelin, which is produced and released mainly by the stomach and functions as an appetite-stimulatory signal. In this study, zebrafish-basedin vivoassays were used to examine whether BPA and five of its analogues, BPAF, BPE, BPC, BPC-CL, and BPS affect appetite regulation. The effect of bisphenol exposure on eating behavior was first examined. Four to six days old zebrafish larvae were exposed to a concentration range of the bisphenols and 17β-estradiol, followed by being fed a stained egg yolk powder at day six. After an hour of feeding, the feed in the gut was imaged by microscopy. Quantitative PCR was used to analyze the gene expression ofleptinandghrelin, as well as eleven other genes involved in appetite control. Exposures to BPA, BPAF, BPE, BPC, BPC-Cl and BPS, resulted in increased amounts of feed in the gut of the larvae in a concentration dependent manner. The qPCR results suggested thatleptinmRNA expression was downregulated with the increasing concentrations of BPA, BPAF and BPC-Cl, whereasghrelinmRNA expression was upregulated. The expression of several additional anorexigenic genes were downregulated by BPAF and BPC-Cl exposure, whereas orexigenic genes were upregulated. In conclusion, bisphenol exposures resulted in an increased eating behavior in zebrafish larvae, which correlated to increased mRNA expression of appetite-stimulatory genes and decreased expression of satiety-inducing genes. In addition, the results suggest that zebrafish larvae can be used to efficiently assess obesogenic capacity of environmental pollutants.
BUB1 inhibition sensitizes lung cancer cell lines to radiotherapy and chemoradiotherapy
Authors: Thoidingjam Shivani , Sriramulu Sushmitha , Hassan Oudai , Brown Stephen L. , Siddiqui Farzan , Movsas Benjamin , Gadgeel Shirish , Nyati Shyam 
Published: April 2024

AbstractBackgroundLung cancer is a major public health concern, with high incidence and mortality. Despite advances in targeted therapy and immunotherapy, microtubule stabilizers (paclitaxel, docetaxel), DNA intercalating platinum drugs (cisplatin) and radiation therapy continue to play a critical role in the management of locally advanced and metastatic lung cancer. Novel molecular targets would provide opportunities for improving the efficacies of radiotherapy and chemotherapy.HypothesisWe hypothesize that BUB1 (Ser/Thr kinase) is over-expressed in lung cancers and that its inhibition will sensitize lung cancers to chemoradiation.MethodsBUB1 inhibitor (BAY1816032) was combined with platinum (cisplatin), microtubule poison (paclitaxel), a PARP inhibitor (olaparib) and radiation in cell proliferation and radiation sensitization assays. Biochemical and molecular assays were used to evaluate their impact on DNA damage signaling and cell death mechanisms.ResultsBUB1 expression assessed by immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in NSCLC and SCLC compared to that of normal tissues. BUB1 overexpression in lung cancer tissues correlated directly with expression of TP53 mutations in non-small cell lung cancer (NSCLC). Elevated BUB1 levels correlated with poorer overall survival in NSCLC and small cell lung cancer (SCLC) patients. A BUB1 inhibitor (BAY1816032) synergistically sensitized lung cancer cell lines to paclitaxel and olaparib. Additionally, BAY1816032 enhanced cell killing by radiation in both NSCLC and SCLC. Molecular changes following BUB1 inhibition suggest a shift towards pro-apoptotic and anti-proliferative states, indicated by altered expression of BAX, BCL2, PCNA, and Caspases 9 and 3.ConclusionA direct correlation between BUB1 protein expression and overall survival was shown. BUB1 inhibition sensitized both NSCLC and SCLC to various chemotherapies (cisplatin, paclitaxel) and targeted therapy (PARPi). Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies.
Complex Regulation of Protocadherin Epigenetics on Aging-Related Brain Health
Authors: Schmithorst Vanessa , Bais Abha , Badaly Daryaneh , Williams Kylia , Gabriel George , Ceschin Rafael , Wallace Julia , Lee Vince , Lopez Oscar , Cohen Annie , Martin Lisa J. , Lo Cecilia , Panigrahy Ashok 
Published: April 2024

AbstractLife expectancy continues to increase in the high-income world due to advances in medical care; however, quality of life declines with increasing age due to normal aging processes. Current research suggests that various aspects of aging are genetically modulated and thus may be slowed via genetic modification. Here, we show evidence for epigenetic modulation of the aging process in the brain from over 1800 individuals as part of the Framingham Heart Study. We investigated the methylation of genes in the protocadherin (PCDH) clusters, including the alpha (PCHDA), beta (PCDHB), and gamma (PCDHG) clusters. ReducedPCDHG, elevatedPCDHA, and elevatedPCDHBmethylation levels were associated with substantial reductions in the rate of decline of regional white matter volume as well as certain cognitive skills, independent of overall accelerated or retarded aging as estimated by a DNA clock. These results are likely due to the different effects of the expression of genes in the alpha, beta, and gamma PCHD clusters and suggest that experience-based aging processes related to a decline in regional brain volume and select cognitive skills may be slowed via targeted epigenetic modifications.
Evidence of compensatory neural hyperactivity in a subgroup of chemotherapy-treated breast cancer survivors and its association with brain aging
Authors: Mulholland Michele M. , Stuifbergen Alexa , De La Torre Schutz Alexa , Franco Rocha Oscar Y. , Blayney Douglas W. , Kesler Shelli R. 
Published: April 2024

AbstractChemotherapy-related cognitive impairment (CRCI) remains poorly understood in terms of the mechanisms of cognitive decline. Neural hyperactivity has been reported on average in cancer survivors, but it is unclear which patients demonstrate this neurophenotype, limiting precision medicine in this population. We evaluated a retrospective sample of 80 breast cancer survivors and 80 non-cancer controls, age 35-73, for which we had previously identified and validated three data-driven, biological subgroups (biotypes) of CRCI. We measured neural activity using the z-normalized percent amplitude of fluctuation from resting state functional magnetic resonance imaging (MRI). We tested established, quantitative criteria to determine if hyperactivity can accurately be considered compensatory. We also calculated brain age gap by applying a previously validated algorithm to anatomic MRI. We found that neural activity differed across the three CRCI biotypes and controls (F = 13.5, p < 0.001), with Biotype 2 demonstrating significant hyperactivity compared to the other groups (p < 0.004, corrected), primarily in prefrontal regions. Alternatively, Biotypes 1 and 3 demonstrated significant hypoactivity (p < 0.02, corrected). Hyperactivity in Biotype 2 met several of the criteria to be considered compensatory. However, we also found a positive relationship between neural activity and brain age gap in these patients (r = 0.45, p = 0.042). Our results indicated that neural hyperactivity is specific to a subgroup of breast cancer survivors and, while it seems to support preserved cognitive function, it could also increase the risk of accelerated brain aging. These findings could inform future neuromodulatory interventions with respect to the risks and benefits of up or downregulation of neural activity.
Dual Bethe-Salpeter equation for the multiorbital lattice susceptibility within dynamical mean-field theory
Authors: van Loon Erik G. C. P. , Strand Hugo U. R. 
Published: April 2024

Dynamical mean-field theory describes the impact of strong local correlation effects in many-electron systems. While the single-particle spectral function is directly obtained within the formalism, two-particle susceptibilities can also be obtained by solving the Bethe-Salpeter equation. The solution requires handling infinite matrices in Matsubara frequency space. This is commonly treated using a finite frequency cutoff, resulting in slow linear convergence. A decomposition of the two-particle response in local and nonlocal contributions enables a reformulation of the Bethe-Salpeter equation inspired by the dual boson formalism. The reformulation has a drastically improved cubic convergence with respect to the frequency cutoff, considerably facilitating the calculation of susceptibilities in multi-orbital systems. This improved convergence arises from the fact that local contributions can be measured in the impurity solver. The dual Bethe-Salpeter equation uses the fully reducible vertex which is free from vertex divergences. We benchmark the approach on several systems including the spin susceptibility of strontium ruthenate Sr2RuO4, a strongly correlated Hund's metal with three active orbitals.

Published by the American Physical Society
2024
Impact Makers (A): The Newman's Own of Management Consulting
Authors: Loutskina Elena , Yemen Gerry , Mead Jenny 
Published: April 2024

This case requires students to evaluate alternative dual-share-class corporate structures that allow companies and entrepreneurs to pursue profit with purpose. The case explores Impact Makers, an IT consulting company based in Richmond, Virginia. While original founders of the firm hold all voting rights, the cash flow rights belong to two nonprofits setting the stage for a Newman's Own model of management consulting. The case discusses whether and how the alternative corporate structure aids the firm's overall strategy to attract top-quality employees, pay them competitive salaries, and provide superior service to its clients while donating 100% of its lifetime value to charitable causes, largely through partnerships with various nonprofit organizations. More importantly, the case asks students to evaluate how such a dual-share-class and dual-purpose company can raise capital to fund continued growth.The case opens with CEO Michael Pirron reminding himself of all the questions he had run through to execute a strategy to further grow Impact Makers' consulting business both through expanding a menu of services and through conquering new geographical markets. To do either, or both, the company needed a cash infusion. Internal cash was limited, as up to 40% of it flowed to charitable partners, demonstrating Impact Makers' commitment to its mission. Raising debt for a company without fixed assets was challenging and time consuming. Complicating it all was that being structured as a nonstock corporation rendered equity raising difficult. Could Impact Makers raise money to grow and stay true to community values at the same time?