bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA expression of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic and asymptomatic primary hyperparathyroidism
Authors: Kaur Parjeet , Hegde Dwijraj , Singh Priyanka , Gautam Dheeraj , Sarin Deepak , Bhadada Sanjay , Mithal Ambrish 
Published: October 2024

Abstract

Background and objective
The exact underlying mechanism for the differential clinical profiles of symptomatic and asymptomatic primary hyperparathyroidism (PHPT) patients has not been fully elucidated, and efforts to define the molecular mechanisms underlying the phenotypic heterogeneity of PHPT have been limited. The aim of this study was to explore the underlying molecular mechanisms involved in the pathogenesis of symptomatic and asymptomatic sporadic PHPT in Asian Indians.

Methods
A prospective cohort study was conducted at a tertiary care hospital in North India. PHPT patients who underwent parathyroidectomy were included. The main outcome was the comparison of vitamin D receptor (VDR), calcium-sensing receptor (CaSR), cyclin D 1 (CD1), and parathyroid hormone (PTH) mRNA levels between symptomatic and asymptomatic PHPT patients and controls determined via quantitative real-time polymerase chain reaction (qRT-PCR).

Results
Forty-two PHPT patients were studied. The mean (SD) age was 49.7 (12.8) years. Twenty patients were asymptomatic. The median PTH levels were significantly greater in the symptomatic group than in the asymptomatic group (878 vs 653 pg/mL). CaSR and VDR mRNAs were significantly lower in both symptomatic and asymptomatic patients than in controls. CD1 and PTH mRNAs were significantly increased in symptomatic patients, but not in asymptomatic PHPT patients compared with controls. Symptomatic PHPT patients had significantly greater CD1 mRNA expression and reduced CaSR expression than asymptomatic patients.

Conclusion
Symptomatic PHPT patients had significantly greater CD1 mRNA expression and lower CaSR expression than asymptomatic patients, underscoring the importance of the molecular mechanisms underlying the phenotypic heterogeneity of PHPT.
Frequency of clinical signs in patients with Cushing's syndrome and mild autonomous cortisol secretion: overlap is common
Authors: Braun Leah T , Vogel Frederick , Nowak Elisabeth , Rubinstein German , Zopp Stephanie , Ritzel Katrin , Beuschlein Felix , Reincke Martin 
Published: October 2024

Abstract

Background
Cushing's syndrome (CS) can be difficult to diagnose. A timely diagnosis, however, is the cornerstone for targeted treatment, to reduce morbidity and mortality. One reason for the difficulties to identify early on patients with CS might be the presence of a mild phenotype. The aim of the study was to classify the phenotypic landscape of CS. We studied patients with overt CS and mild autonomous cortisol secretion (MACS).

Method
The study was part of the German Cushing's registry. Patients were prospectively included at time of diagnosis and the number of comorbidities and clinical signs and symptoms were assessed in a standardized fashion. One hundred twenty-nine patients with CS (pituitary CS, n = 85, adrenal CS, n = 32, ectopic CS, n = 12, respectively) and 48 patients with MACS were included. Patients with clinical signs and/or comorbidities typical for CS and at least 2 pathological screening tests were classified as having CS. Patients with a 1 mg low-dose-dexamethasone-suppression test above 1.8 µg/dL without being clinically overt CS were classified as having MACS.

Results
On average, patients with CS had 2 comorbidities (range 1-3) at time of diagnosis (pituitary CS: 2 [1-3], adrenal CS: 3 [2-4], ectopic CS: 3 [2-4]). Patients with MACS, however, had 3 comorbidities (range 2-3). Hypertension was the most common comorbidity in all subtypes of CS (78%-92%) and in patients with MACS (87%). Of a total of 11 clinical signs, patients with CS had on average 5 with 28% of patients having between 0 and 3 clinical signs, 50% 4-7 signs, and 22% more than 7 clinical signs. Patients with MACS had on average 2 clinical signs (range 1-3) at time of diagnosis.

Conclusion
The phenotypic landscape of CS is quite variable. The frequency of comorbidities is similar between patients with CS and MACS. A relevant number of patients with overt CS have just a few clinical signs. There is also an overlap in frequency of symptoms and clinical signs between patients with CS and MACS. According to the current guidelines, 96% of our patients with MACS fall into the category “consideration of adrenalectomy”. This should be kept in mind when making treatment decisions in the latter group of patients.
Ileoanal Pouch–Related Fistulas: A Narrative Review
Authors: Bronze Sergio , Kayal Maia , Estevinho Maria Manuela , Hahn Sue , Khaitov Sergey , Colombel Jean-Frederic , Wong Serre-Yu 
Published: October 2024

Abstract
Ileoanal pouch–related fistula (IAPRF) is a possible complication after ileal pouch-anal anastomosis that significantly impacts pouch prognosis and the patient’s quality of life. This study aimed to perform a comprehensive narrative review to better classify the epidemiology, risk factors, etiology, management, and outcomes of IAPRF, and to propose an algorithm for its systematic classification. Ten studies comprising 664 patients with IAPRF were identified, with a prevalence ranging from 4% to 45%. The reported fistula types were as follows: pouch-vaginal (n = 236, 35.5%), perineal (n = 139, 21%), enterocutaneous (n = 54, 8%), pouch-anal (n = 53, 8%), presacral (n = 18, 2%), and anastomotic (n = 15, 2%). Postsurgical pelvic sepsis occurred in 21%-37.2% of patients. Twenty additional studies regarding fistula classification divided them according to onset time and etiology, defining 5 categories: anastomotic-related, technical aspects of the surgery, Crohn’s disease–like pouch inflammation, cryptoglandular, and malignancy. Pouch excision was reported in up to 70% of patients. Fistulas associated with anastomotic complications, technical surgical issues, and cryptoglandular fistulas warrant surgical management. On the other hand, fistulas associated with inflammation are preferentially managed with biologics or small molecules.
Associations Between Histo-blood Group Antigen Status in Mother-Infant Dyads and Infant Oral Rotavirus Vaccine Immunogenicity in Rural Zimbabwe
Authors: Pun Joshua , Evans Ceri , Chasekwa Bernard , Church James A , Gough Ethan , Mutasa Kuda , Rukobo Sandra , Govha Margaret , Mushayanembwa Patience , Majo Florence D , Tavengwa Naume V , Humphrey Jean H , Kirkpatrick Beth D , Kosek Margaret , Ntozini Robert , Prendergast Andrew J 
Published: October 2024

Abstract

Background
Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe.

Methods
We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs. Serum anti-rotavirus immunoglobulin A was measured by enzyme-linked immunosorbent assay. We explored adjusted associations between FUT2/FUT3 status and RVV seroconversion (primary outcome, n = 322) and seropositivity and geometric mean titer (secondary outcomes, n = 776).

Results
Infants of FUT2- or FUT3-positive women were less likely to seroconvert post-RVV than infants of FUT2- or FUT3-negative women (FUT2 positive [20.1%] vs FUT2 negative [27.5%]: adjusted relative risk [aRR], 0.47; 95% CI, .26–.82; P = .008; FUT3 positive [18.1%] vs FUT3 negative [30.0%]: aRR, 0.45; 95% CI, .25–.78; P = .005). When compared with FUT2-positive infants with FUT2-positive mothers, FUT2-positive infants with FUT2-negative mothers were twice as likely to seroconvert (36.8% vs 21.9%; aRR, 2.12; 95% CI, 1.23–3.63; P = .006). When compared with FUT3-positive infants with FUT3-positive mothers, FUT3-positive infants with FUT3-negative mothers were 3 times as likely to seroconvert (48.3% vs 18.2%; aRR, 2.99; 95% CI, 1.82–4.90; P &lt; .001).

Conclusions
Maternal and infant FUT2 and FUT3 status influences infant RVV immunogenicity.
Anarchy and Empire: World-Conquerors and International Systems
Authors: Phillips Andrew , Sharman J C 
Published: October 2024

Abstract
Why are some international systems characterized by stable multipolarity while elsewhere conquest produces universal empires? We explain this variation through contrasting the conventional story of the consolidation of multipolar anarchy in Europe against the Ottoman conquest of the Near East and the Manchu conquest of greater China. Both the Ottomans and the Manchus developed the capacity for systemic conquest via hybridizing steppe and sedentary military techniques. Furthermore, both surmounted the legitimation gradient of conquest. The Ottomans and Manchus used cultural statecraft to prevent balancing coalitions and encourage bandwagoning and collaboration. Cultural statecraft comprised strategies of co-opting preexisting symbols of imperial rule and employing multivocal legitimacy strategies to sequentially appeal to multiple segmented audiences. In Europe, both military obstacles and religious confessional ideational divisions frustrated would-be conquerors. Multipolar anarchy is thus a contingent outcome in international politics rather than a constant, which can be extinguished by militarily powerful and culturally agile “world conquerors.”
Situatedness and distantiation: education in a time of ecological and climate crises
Authors: Kvamme Ole Andreas 
Published: October 2024

Abstract
In this article, I explore the significance of place in education. The historical context is expressed by the ecological and climate crises in a world distinguished by the unjust distribution of privileges and burdens. I elucidate the concept of place by entering the tradition of the pedagogy of place. Here, the significance of place is accentuated with a sensitivity to the local context, in contrast to other educational approaches that emphasize more generic, abstract knowledge. A central premise is the notion of place as a delimited unit that is distinguished from other places. This stable notion, I argue, needs to be reconsidered in the present. With reference to Massey, I accentuate relations as pivotal to a notion of place that accommodates both a sense of belonging and conflicts of power and interest. I hold that education at this time in history should be sensitive to our situatedness in everyday life’s web of relationships. Still, general knowledge is required to bring up perspectives that enable students to critically conceive the place in which they are situated. I make and discuss these claims with reference to and in critique of Young’s notion of powerful knowledge and Klafki’s reformulation of German Didaktik. A central concern is to clarify the mediation of situated knowledge and general knowledge in educational practice. In the final part of the article, I bring in elements from critical hermeneutics and utopian thinking, approaching Bildung as a process involving situatedness, distantiation, and refiguration.
Double distal corporal anchoring stitch for lateral penile implant cylinder extrusion
Authors: Raheem Omer A , Kalidoss Senthooran , Pomar Hector Alejandro , Suarez-Sarmiento Jr Alfredo , Perito Paul 
Published: October 2024

Abstract

Background
The ventral and distal aspects of the corpora cavernosa are the thinnest, increasing the likelihood of cylinder extrusion or crossover complications pertaining to inflatable penile prosthesis procedures. A double distal corporal anchoring double stitch can be used to robustly secure impending lateral extrusions and crossovers of implant cylinders. It is a novel, effective corrective measure for the uncommon complication of migrated cylinders in inflatable penile prosthesis placement.

Aim
To describe the surgical indications and technique for the double distal corporal anchoring fixation stitch for lateral penile implant cylinder extrusion.

Methods
We discuss a double-stitch technique that is performed following corporoplasty and capsulotomy. A lateral incision is made subcoronally on the affected side to identify the crossover or lateral extrusion. The cylinder is repositioned properly within the native corpora to prevent further cylinder migration. Two 2-0 Ethibond sutures are threaded through the distal cylinder eyelet, and each suture is delivered through the glans with a Keith needle and tied off. An incision is made in the glans, and 1 arm of each suture is tied with the other to create a bridge between the sutures that can be positioned deep within the skin of the glans.

Outcomes
Over the past 4 years, 66 patients with lateral cylinder extrusion underwent the double distal corporal anchoring fixation stitch procedure, with overall improved satisfaction (97%). Only 2 patients had surgical complications. One patient experienced repeated lateral extrusion of the penile implant cylinders 6 weeks following the double-anchoring stitches procedure. The second patient developed a painful suture granuloma that necessitated excision, which resolved this issue, and the penile implant cylinder remained in the proper position over a year later.

Clinical Implications
This technique ensures the secure fixation of the affected cylinders in the surgical capsule by creating a bridge between 2 sutures holding each repositioned cylinder in place, and the ensuing fibrotic reaction helps to fixate the extruded cylinder within the midglandular tissue.

Strength and Limitations
This surgical technique describes the double distal corporal anchoring stitch for lateral penile implant cylinder extrusion. Further studies are warranted to validate long-term outcomes and satisfaction.

Conclusion
The double distal corporal anchoring fixation stitch is a safe and efficacious method to secure cylinders in the proper surgical capsule during revision procedures to correct distal crossovers or laterally extruded penile prosthesis implants.
Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with lomustine/temozolomide
Authors: Zeyen Thomas , Böhm Laura , Paech Daniel , Schäfer Niklas , Tzaridis Theophilos , Duffy Cathrina , Nitsch Louisa , Schneider Matthias , Potthoff Anna-Laura , Schneider-Rothhaar Javen Lennard , Steinbach Joachim Peter , Hau Peter , Kowalski Thomas , Seidel Clemens , Krex Dietmar , Grauer Oliver , Goldbrunner Roland , Zeiner Pia Susan , Tabatabai Ghazaleh , Galldiks Norbert , Stummer Walter , Hattingen Elke , Glas Martin , Gkika Eleni , Vatter Hartmut , Radbruch Alexander , Herrlinger Ulrich , Weller Johannes , Schaub Christina 
Published: October 2024

Abstract

Background
Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The response assessment in neuro-oncology (RANO) resects group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyze the prognostic performance of binary EOR assessment compared to volumetric assessment.

Methods
Seventy-eight patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and progression-free survival was analyzed using uni- and multivariable Cox regression analysis as well as two-sided log-rank test. Patients were divided into residual tumor volume (RTV) ≤1 cm³, &gt;1–≤5 cm³, and &gt;5 cm³ following the proposed criteria of the RANO resect group.

Results
Prolonged OS was associated with age &lt;60 years, low RTV, and gross total resection. RTV had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤ 1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI: 46.94–not reached), with a 5-year survival rate of 49%.

Conclusions
Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.
Temporal Dynamics of Nucleus Accumbens Neurons in Male Mice During Reward Seeking
Authors: Schall Terra A. , Li King-Lun , Qi Xiguang , Lee Brian T. , Wright William J. , Alpaugh Erin E. , Zhao Rachel J. , Liu Jianwei , Li Qize , Zeng Bo , Wang Lirong , Huang Yanhua H. , Schlüter Oliver M. , Nestler Eric J. , Nieh Edward H. , Dong Yan 
Published: October 2024

AbstractThe nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable “free-willed” animals to obtain rewards remain elusive. Here, we recorded Ca2+activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca2+activity: approximately 0, -2.5 or -5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at -5 sec or D2-neurons at -2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior.
Synchronized Chromatin Organization Serves as Potent Biomarker in Anaesthesia-based Plant Consciousness
Authors: Chandra Shilpa , Mukherjee Bodhidipra , Salam Abdul , Anjum Farhan , Nandi Chayan Kanti , Behera Laxmidhar 
Published: October 2024

AbstractAnaesthesia has been used for centuries for medical purposes. With the application of anaesthesia, organisms lose their conscious awareness. It provides a temporary loss of sensation, which enables painless performance during surgery. However, the cellular mechanisms underlying the effects of anaesthesia are not clearly understood. It has been proposed that plant root function is analogous to the human brain. Here, using super-resolution imaging technique, we explored an organelle-level understanding of the effect of anaesthesia on plant roots and the stem connecting to the root. Our results showed that the nuclei organized themselves in an orchestrated manner upon treatment with both local and general anaesthesia without damaging their structure. Euchromatin within the nucleus was found to be reorganized in the nuclear periphery, and this process was found to be independent of ATP. In contrast, mitochondria, microtubules, endocytic vesicles, and chloroplasts, which are other important organelles in plant cells, were highly altered or damaged under the same experimental conditions. Eventually, the cellular homeostasis again maintained and process is reversible upon the removal of anaesthesia. Our results suggest that such orchestrated chromatin organization without disturbing the overall structure of the nucleus could be used as a potent biomarker for conscious awareness in plants.Graphical Abstract
Damage-induced IL-18 stimulates thymic NK Cells limiting endogenous tissue regeneration
Authors: Granadier David , Cooper Kirsten , Kousa Anastasia , Acenas Dante , Lemarquis Andri , Hernandez Vanessa , Warren Makya , Iovino Lorenzo , deRoos Paul , Lederer Emma E. , Shannon-Sevillano Steve , Kinsella Sinéad , Evandy Cindy , Brink Marcel R.M. van den , Dudakov Jarrod A. 
Published: October 2024

ABSTRACTInterleukin-18 is an acute phase pro-inflammatory molecule crucial for mediating viral clearance by activating Th1 CD4+, cytotoxic CD8+T, and NK cells. Here, we show that mature IL-18 is generated in the thymus following numerous distinct forms of tissue damage, all of which cause caspase-1-mediated immunogenic cell death. We report that IL-18 stimulated cytotoxic NK cells limit endogenous thymic regeneration, a critical process that ensures restoration of immune competence after acute insults like stress, infection, chemotherapy, and radiation. NK cells suppressed thymus recovery by aberrantly targeting thymic epithelial cells (TECs), which act as the master regulators of organ function and regeneration. Together these studies reveal a novel pathway regulating tissue regeneration in the thymus and offer IL-18 as a potential therapeutic target to boost thymic function. Moreover, given the enthusiasm for IL-18 as a cancer immunotherapy for its capacity to elicit a type-1 immune response, these findings also offer insight into potential off-target effects.
Redox Signaling Mediates Differentiation of Adipose Progenitors in Response to Inflammatory Cytokines in the Adipose Tissue Secretome
Authors: Wager Jessica L. , Baker Larissa G. , Scheidl Taylor B. , Yonan Sophie Z. , Colarusso Pina , Dufour Antoine , Thompson Jennifer A. 
Published: October 2024

ABSTRACTAdipogenesis, the terminal differentiation of adipose progenitor cells (APCs), is critical in maintaining the functional integrity of adipose depots under obesogenic conditions. It is thought that a signal arising from the adipose microenvironment triggers APC differentiation; yet the identity and source of the signal remains unknown. This study sought to uncover the signal responsible for activating adipogenesis. Redox signaling was shown to influence adipogenesis in primary murine APCs treated with pharmacologic agents to manipulate the levels of reactive oxygen species (ROS). Increased generation of superoxide (O2-) and hydrogen peroxide (H2O2)viaredox cyclers amplified both early and late APC differentiation, while ROS scavengers and antioxidants blunted differentiation. The impact of specifically targeting H2O2with the antioxidant, catalase, or a catalase inhibitor, was restricted to lipid accumulation in late adipogenesis. Protein was concentrated from conditioned media of adipose tissue explants culturedex vivoto capture signals within the adipose secretome. Differentiation was enhanced in APCs cultured in the presence of the adipose secretome, an effect that was diminished with scavenging of ROS and amplified when the secretome was collected from mice fed a high fat diet for 8 weeks. Proteomic analysis revealed that the adipose secretome from animals on a high fat diet was enriched in pathways related to immune cell-mediated inflammation, with interleukin 6 (IL-6) as a central regulator of differentially expressed proteins. A multiplex assay to measure cytokines confirmed higher IL-6 in the adipose secretome of high fat-fed animals. Exposure of APCs to IL-6 increased adipogenesis, while treatment of APCs with an IL-6 blocking antibodies diminished the adipogenic effect of the adipose secretome. Together, these findings substantiate a role for redox signaling in the regulation of adipogenesis and identify IL-6 as a novel activator of adipogenesis that may mediate APC differentiation via generation of ROS under obesogenic conditions.