bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interplay of immunity and growth: a case of combined variable immunodeficiency and growth hormone deficiency
Authors: Majety Sameer K. , Modh Sagar , Mishra Devrakshita , Alam Nafisa , Suvvari Tarun K. , Pagadala Chandra G.M. , Muppana Gopichand 
Published: September 2024

Introduction:
Common variable immunodeficiency (CVID) is one of the more common immunodeficiencies seen in clinical practice with a complex disease pathology; while growth hormone deficiency (GHD) is a disorder characterized by complete or relative absence of the human growth hormone.

Case presentation:
This case report presents a 13-year-old female patient with a long history of recurrent respiratory tract and ear infections, along with a notable failure to hit her developmental milestones early in the second decade of her life. The diagnosis was based on a thorough investigation of serum immunoglobulins for CVID and a GH stimulation test for GHD. For these, the patient was placed on a tailored regimen of IVIGs, somatropin therapy, and antibiotics for the recurrent infections.

Case discussion:
CVID patients characteristically present with recurrent respiratory and ear infections, showing a marked decrease in immunity. Often diagnosed in childhood, GHD typically presents as growth failure along with developmental delays in dentition. There has been a notable rise in the coexistence of immunodeficiency syndromes and endocrinopathies studied in the past few decades. The case highlights and discusses the complex underlying pathology at play that links the two conditions to each other, while also excluding the various differentials.

Conclusion:
The report highlights the various challenges faced by both clinicians and patients when dealing with dual health conditions that may have a relatively nonspecific presentation. Some of which include the diagnostic difficulties, financial strains on the patient leading to poor follow-up, and in the long-term, the development of various complications. This emphasizes the importance of early disease diagnosis and strict management protocols for the said disease, for the overall betterment of the patient’s quality of life.
A young female’s battle with toxic epidermal necrolysis induced by NSAIDs: a case report
Authors: Adhikari Pratik , Singh Uday , Yadav Pramodman S. , Shah Leeza , Dev Abinash , Mandal Subhash C. 
Published: September 2024

Introduction:
Stevens-Johnson Syndrome (SJS) is a rare but severe mucocutaneous reaction often triggered by medications or infections, characterized by extensive epidermal detachment and mucosal involvement. This condition poses a high risk of morbidity and mortality, requiring prompt recognition and treatment.

Case presentation:
An 18-year-old Asian female from eastern Nepal presented with nonitchy red spots, high fever, and significant discomfort following the administration of ibuprofen for minor sores. She developed extensive skin involvement covering 25% of her body surface area and severe mucosal lesions. Laboratory investigations revealed anemia, leukocytosis, and coagulopathy. She was admitted to the ICU, where she received broad-spectrum antibiotics, corticosteroids, and supportive care. The patient also developed acute kidney injury during treatment but eventually recovered and was discharged after a week.

Clinical discussion:
The rapid onset of SJS in this patient reveals the unpredictable nature of drug-induced reactions. Early intervention with a multidisciplinary approach involving dermatology, intensive care, and infectious disease specialists was crucial in managing her condition. Despite the controversy surrounding corticosteroid use in SJS, their administration likely contributed to the rapid improvement in inflammation and skin healing. The case highlights the importance of early recognition, prompt management, and careful monitoring for adverse drug reactions, especially when prescribing medications known to cause SJS.

Conclusion:
The successful outcome achieved through a multidisciplinary approach provides valuable insights into the effective strategies for handling severe drug reactions, emphasizing that early diagnosis and comprehensive management in patients with SJS is critical.
Acute primary gastric volvulus with open suture gastropexy: a case report
Authors: Behboudi Behnam , Hassanpour Saeed , Fazeli Mohammad Sadegh , Tadbir-Vajargah Kiana 
Published: September 2024

Introduction and importance:
Gastric volvulus is rare and may result in a closed-loop obstruction. Even with appropriate management, mortality may occur in up to 50% of patients. The conventional treatment for acute gastric volvulus has been immediate operation with reduction and detorsion of the volvulus.

Case presentation:
Here, the authors present a case of acute gastric volvulus following fasting. The patient underwent definitive surgical treatment with detorsion and gastropexy, and was discharged with no postoperative complications.

Clinical discussion:
Acute gastric volvulus is a rare yet serious medical condition that requires immediate diagnosis and intervention to prevent complications. The case presented highlights the importance of recognizing both common and subtle signs of gastric volvulus, though nonspecific symptoms may delay diagnosis. In this patient, the acute onset of symptoms following a large meal and failure to pass a nasogastric tube were early indicators that prompted imaging and led to the diagnosis of mesenteroaxial gastric volvulus. CT imaging played a crucial role in confirming the diagnosis, demonstrating its value in acute abdominal presentations where symptoms overlap with other causes of gastrointestinal obstruction. This case also emphasizes the importance of early intervention to avoid ischemic complications and improve survival rates.

Conclusion:
Acute gastric volvulus is a rare, potentially life-threatening condition that can easily be missed due to nonspecific symptoms. Early recognition, prompt imaging, and immediate surgical intervention are critical to preventing serious complications such as strangulation and necrosis.
Hyperchloremia and Prolonged Acidosis During Treatment for Pediatric Diabetic Ketoacidosis
Authors: Yıldırımçakar Didem , Öcal Murat , Altıncık Selda Ayça , Özhan Bayram 
Published: September 2024

Objectives
Diabetic ketoacidosis (DKA) is characterized by metabolic acidosis with a high anion gap secondary to ketonemia. Intravenous hydration fluids used in treatment can cause chloride overload, leading to hyperchloremic metabolic acidosis (HMA). The development of HMA can lead to the persistence of acidosis despite the resolution of ketonemia.

Methods
A total of 178 DKA episodes in 153 patients treated between January 2013 and October 2023 were included in the study. Creatine-based glomerular filtration rate and HbA1c value at admission and venous blood gas parameters (pH, actual bicarbonate, base deficit), anion gap, chloride-corrected bicarbonate, nonchloride base deficit, and sodium and chloride measured at 0, 2, 4, 6, 9, 12, 18 and 24 hours were evaluated.

Results
Hyperchloremia was detected in 69.3% of participants and developed at a mean of 6.3 (±4.3) hours of treatment. The incidence of hyperchloremia increased with the duration of treatment; the rates were 8.4%, 51.3%, 65%, 76.2%, 75.5%, and 80% at 0, 6, 9, 12, 18, and 24 hours of treatment, respectively. The group with hyperchloremia had more severe acidosis, a higher HbA1c value, and a longer resolution time. At the 12th hour of treatment, acidosis continued based on pH and HCO3 levels, whereas the hyperchloremia group exhibited a low anion gap (mean 12.8). At the 6th hour of treatment, the resolution rates were significantly lower in the hyperchloremia group based on the pH and HCO3 levels but increased when assessed by chloride-corrected HCO3 and anion gap.

Conclusions
During treatment of DKA, monitoring anion gap, blood ketones, and Cl−/Na+ ratio or using regression equations in addition to routine acid-base parameters may help differentiate DKA from HMA and prevent prolonged intravenous treatment.
Trapezius Island Myocutaneous Flap for Head, Neck, and Facial Reconstruction in Neurofibromatosis Type 1-Associated Plexiform Neurofibromas
Authors: Chen Wei-liang , Zhou Bin , Huang Zi-xian , Lin Dao-wei , Zhang Jie-ming 
Published: September 2024

Background:
Reconstruction of significant soft tissue defects in the head and neck region after resection of extensive plexiform neurofibromas, as well as preservation and restoration of cosmetic and functional aspects, presents a considerable challenge.

Aims:
The purpose is to evaluate the feasibility of eTMF in repairing substantial defects after the complete resection of NF1 PN.

Patients and Methods:
Patients diagnosed with substantial neurofibromatosis (NP) type 1 (NF1), according to the revised criteria, underwent complete resection and remodeling of the facial aesthetic unit. An extended vertical lower trapezius island myocutaneous flap (eTIMF) was used for the defect reconstruction. Perioperative complications were evaluated using the Clavien-Dindo classification. ECOG PS was assessed. Postoperative follow-up at 6 months and completion of UW-QOL. The questionnaire included swallowing, chewing, speech, and quality of life scores. Two patients had pathogenic missense variants: c.5609G>A (p.Arg1870Gln) in exon 38 of NF1 in the first case, and c.4600C>T (p.Arg1534*) in exon 35 in the second case.

Results:
Two eTMFs were harvested successfully. Five facial esthetic units were remodeled, and 4 units were remodeled. Two extensive tumors were nearly entirely removed. No severe complications were noted. The ECOG PS improved from grade 3 in the first week postsurgery to grade 0 by the eighth week. The UW-QOL results indicated that swallowing, chewing, and speaking functions returned to their preoperative levels, with a 40% improvement in quality of life, reaching 60% and 80%, respectively.

Conclusions:
eTMF to repair substantial defects following total resection of NF1 PN and facial esthetic unit remodeling enhances appearance, function, and psychosocial outcomes. This technique is safe, efficient, resource-conserving, and simple to implement.
Early and Late Microvascular Inflammation Have Differing Etiological Causes and Clinical Expression
Authors: Nankivell Brian J. , Viswanathan Seethalakshmi 
Published: September 2024

Background.
Microvascular inflammation (MVI) is an important pathological feature of antibody-mediated rejection (AMR). How posttransplant time affects its clinicopathological expression is little understood.

Methods.
This retrospective, single-center study screened 3398 kidney transplant biopsies and dichotomized 202 MVI ≥ 2 (Banff glomerulitis + peritubular capillaritis ≥ 2) samples by 9-mo median incidence time for comparison.

Results.
The prevalence of MVI ≥ 2 was 12.4% in transplant kidneys, which failed more frequently than propensity-matched normal controls (n = 202; P < 0.001). Epidemiological risk factors for early MVI ≥ 2 were delayed graft function, prior AMR, and circulating donor-specific antibodies (DSAs+). Prior recipient sensitization occurred in 72.3%. Early MVI ≥ 2 was classified AMR in 65.3% and cellular rejection in 34.7%, and demonstrated excellent functional recovery and graft survival comparable to normal control kidneys. Late MVI ≥ 2 was predicted by younger (18 = 29 y) age, female recipient, living-donation, prior methylprednisolone, cyclosporine (versus tacrolimus, levels <5 ng/mL), absent antiproliferative therapy, and DSA+ using multivariable epidemiological modeling. Nonadherence caused 49.5%, with iatrogenic minimization responsible for 47.5%, usually for recipient infection. Late MVI ≥ 2 was because of AMR in 93.1%, and characterized by greater interstitial fibrosis, tubular atrophy, complement degradation split-product 4d (C4d) staining of peritubular capillaries+, endothelial C4d staining of glomerular capillaries+, transplant glomerulopathy and vasculopathy scores, DSA strength, and graft failure than early MVI ≥ 2 or normal transplant kidneys. Death-censored graft survival in 149 unique MVI ≥ 2 kidneys was independently determined by nonadherence, serum creatinine, proteinuria, DSA+, Banff C4d staining of peritubular capillaries+, and chronic interstitial fibrosis scores. MVI score and time lost significance using multivariable Cox regression.

Conclusions.
The changing expression of MVI ≥ 2 over time is best explained by differences in underimmunosuppression and microvascular injury from AMR impacting allograft function and survival.
Parental care modifies the role of early-life size and growth in shaping future physiology
Authors: Laubach Zachary M. , Madden Sage A. , Pardue Aleea , Safran Rebecca J. 
Published: September 2024

ABSTRACTSize and growth early in life are associated with physiological development and these traits influence fitness. Life history theory predicts that the relationship between traits reflect constraints involving allocation and acquisition of resources. Using longitudinal data from 113 wild nestling barn swallows (Hirundo rustica erythrogaster), we first characterized developmental changes in glucose metabolism, a physiological trait involved in energy mobilization and response to stress. Next, we used these data to test hypotheses from life history theory about allocation and acquisition of resources based on associations of nestling size and growth with glucose physiology and assessed whether these relationships are modified by parental care. We found that larger nestlings had higher baseline blood glucose and larger magnitude of change in glucose in response to a stressor. Further, this relationship was most pronounced among birds in nests that received the lowest amount of parental care. Given that glucose metabolism fuels activity and is critical in the vertebrate stress response, these results suggest that physiological constraints may contribute to the early-life disadvantage of being smaller, especially in the context of lower parental care. While these findings are inconsistent with a trade-off involving differential allocation of resources between life history traits, they align with the differential acquisition hypothesis.
Activation mapping in multi-center rat sensory-evoked functional MRI datasets using a unified pipeline
Authors: Galteau Marie E , Broadwater Margaret , Chen Yi , Desrosiers-Gregoire Gabriel , Gil Rita , Kaesser Johannes , Kim Eugene , Kıryağdı Pervin , Lambers Henriette , Liu Yanyan Y , López-Gil Xavier , MacNicol Eilidh , Mohebkhodaei Parastoo , De Oliveira Ricardo X N. , Pereira Carolina A. , Reimann Henning M , Rivera-Olvera Alejandro , Selingue Erwan , Sirmpilatze Nikoloz , Strobelt Sandra , Sumiyoshi Akira , Tham Channelle , Tudela Raul , Vrooman Roël M. , Wank Isabel , Zhang Yongzhi , van Engelenburg Wessel A , Baudewig Jürgen , Boretius Susann , Cash Diana , Chakravarty M Mallar , Chuang Kai-Hsiang , Ciobanu Luisa , Devenyi Gabriel A , Faber Cornelius , Hess Andreas , Homberg Judith R , Jelescu Ileana O , Justicia Carles , Kawashima Ryuta , Niendorf Thoralf , Scheenen Tom WJ , Shemesh Noam , Soria Guadalupe , Todd Nick , Wachsmuth Lydia , Yu Xin , Zhang Baogui B , Shih Yen-Yu Ian , Lee Sung-Ho , Grandjean Joanes 
Published: September 2024

AbstractFunctional Magnetic Resonance Imaging (fMRI) in rodents is pivotal for understanding the mechanisms underlying Blood Oxygen Level-Dependent (BOLD) signals and phenotyping animal models of disorders, amongst other applications. Despite its growing use, comparing rodent fMRI results across different research sites remains challenging due to variations in experimental protocols. Here, we aggregated and analyzed 22 sensory-evoked rat fMRI datasets from 12 imaging centers, totaling scans from 220 rats, to assess the consistency of results across diverse protocols. We applied a standardized preprocessing pipeline and evaluated the impact of different hemodynamic response function models on group and individual level activity patterns. Our analysis revealed inter-dataset variability attributed to differences in experimental design, anesthesia protocols, and imaging parameters. We identified robust activation clusters in all (22/22) datasets. The comparison between stock human models implemented in software and rat-specific models showed significant variations in the resulting statistical maps. Our findings emphasize the necessity for standardized protocols and collaborative efforts to improve the reproducibility and reliability of rodent fMRI studies. We provide open access to all datasets and analysis code to foster transparency and further research in the field.
Early adipose tissue wasting in a novel preclinical model of human lung cancer cachexia
Authors: Snoke Deena B. , van der Velden Jos L. , Bellafleur Emma R. , Dearborn Jacob S. , Lenahan Sean M. , Heininger Skyler C. J. , Ather Jennifer L. , Sarausky Hailey , Stephenson Daniel , Reisz Julie A. , D’Alessandro Angelo , Majumdar Devdoot , Ahern Thomas P. , Sandler Kim L. , Landman Bennett A. , Janssen-Heininger Yvonne M.W. , Poynter Matthew E. , Seward David J. , Toth Michael J. 
Published: September 2024

AbstractCancer cachexia (CC), a syndrome of skeletal muscle and adipose tissue wasting, reduces responsiveness to therapies and increases mortality. There are no approved treatments for CC, which may relate to discordance between pre-clinical models and human CC. To address the need for clinically relevant models, we generated tamoxifen-inducible, epithelial cell specificKrasG12D/+(G12D) mice.G12Dmice develop CC over a protracted time course and phenocopy tissue, cellular, mutational, transcriptomic, and metabolic characteristics of human lung CC. CC inG12Dmice is characterized by early loss of adipose tissue, a phenotype confirmed in a large cohort of patients with lung cancer. Tumor-released factors promote adipocyte lipolysis, a driver of adipose wasting in human CC, and adipose tissue wasting was inversely related to tumor burden. Thus,G12Dmice model key features of human lung CC and suggest a novel role for early adipose tissue wasting in CC.
UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment by regulating tumour cell fate
Authors: Suwa Tatsuya , Lee Kelly , Chai Ian , Clark Heather , MacLean David J. , Machado Nicole , Rodriguez Berriguete Gonzalo , Higgins Geoff S , Hammond Ester M , Olcina Monica M 
Published: September 2024

AbstractDysregulation of the C5a-C5a receptor 1 (C5aR1) signalling axis underlies inflammation and immune-driven pathology. C5aR1 was traditionally thought to be primarily expressed on the cell membrane, although recent reports indicate the importance of intracellular C5aR1 expression for the inflammatory effector functions of various cell types. However, the mechanisms regulating C5aR1 expression and localisation remain unclear. In tumours with an immunosuppressive microenvironment, we recently found robust C5aR1 expression on malignant epithelial cells, highlighting potential tumour cell–specific functions. Here, we show that hypoxia, a hallmark of immunosuppressive microenvironments, induces C5aR1 expression in an unfolded protein response (UPR)-dependent manner via enhanced endoplasmic reticulum stress. Furthermore, hypoxia drives endocytosis, relocating C5aR1 from the cell membrane to the intracellular compartment. By genetically and pharmacologically targeting the C5a/C5aR1 axis, we show that C5aR1 mediates cellular adaptation to hypoxia by regulating processes associated with cell fate, including autophagy and apoptosis. In line with hypoxia-induced intracellular C5aR1 pools, pharmacological inhibition of C5aR1, particularly with cell-permeable small molecule inhibitors, significantly reduces tumour cell survival. These results suggest that the dysregulated C5a/C5aR1 axis and the hypoxia-induced shift in C5aR1 localisation, support tumour cell survival and provide new insights into therapeutic strategies for targeting the C5a/C5aR1 axis.
Gut colonization ofEnterococcusspecies is associated with COVID-19 disease in Uganda
Authors: Agudelo Carolina , Kateete David Patrick , Nasinghe Emmanuel , Kamulegeya Rogers , Lubega Christopher , Mbabazi Monica M , Baker Noah , Lin Kathryn , Liu Chang C. , Kasambula Arthur Shem , Kigozi Edgar , Komakech Kevin , Mukisa John , Mulumba Kassim , Mwachan Patricia , Nakalanda Brenda Sharon , Nalubega Gloria Patricia , Nsubuga Julius , Sitenda Diana , Ssenfuka Henry , Cirolia Giana , Gustafson Jeshua T. , Wang Ruohong , Nsubuga Moses Luutu , Yiga Fahim , Stanley Sarah A. , Bagaya Bernard Ssentalo , Elliott Alison , Joloba Moses , Wolf Ashley R. 
Published: September 2024

AbstractBackgroundInfection with the COVID-19-causing pathogen SARS-CoV-2 is associated with disruption in the human gut microbiome. The gut microbiome enables protection against diverse pathogens and exhibits dysbiosis during infectious and autoimmune disease. Studies based in the United States and China have found that severe COVID-19 cases have altered gut microbiome composition when compared to mild COVID-19 cases. We present the first study to investigate the gut microbiome composition of COVID-19 cases in a population from Sub-Saharan Africa. Given the impact of geography and cultural traditions on microbiome composition, it is important to investigate the microbiome globally and not draw broad conclusions from homogenous populations.ResultsWe used stool samples in a Ugandan biobank collected from COVID-19 cases during 2020-2022. We profiled the gut microbiomes of 114 symptomatic individuals who tested positive for SARS-CoV-2 along with 76 household contacts who did not present any symptoms of COVID-19. The inclusion of healthy controls enables us to generate hypotheses about bacterial strains potentially related to susceptibility to COVID-19 disease, which is highly heterogeneous. Comparison of the COVID-19 patients and their household contacts revealed decreased alpha diversity and blooms ofEnterococcusandEggerthellain COVID-19 cases.ConclusionsOur study finds that the microbiome of COVID-19 individuals is more likely to be disrupted, as indicated by decreased diversity and increased pathobiont levels. This is either a consequence of the disease or may indicate that certain microbiome states increase susceptibility to COVID-19 disease. Our findings enable comparison with cohorts previously published in the Global North, as well as support new hypotheses about the interaction between the gut microbiome and SARS-CoV-2 infection.