bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered desensitization and internalization patterns of rodent versus human glucose‐dependent insulinotropic polypeptide (GIP) receptors. An important drug discovery challenge
Authors: Gasbjerg Lærke Smidt , Rasmussen Rasmus Syberg , Dragan Adrian , Lindquist Peter , Melchiorsen Josefine Ulrikke , Stepniewski Tomasz Maciej , Schiellerup Sine , Tordrup Esther Karen , Gadgaard Sarina , Kizilkaya Hüsün Sheyma , Willems Sabine , Zhong Yi , Wang Yi , Wright Shane C. , Lauschke Volker M. , Hartmann Bolette , Holst Jens Juul , Selent Jana , Rosenkilde Mette Marie
Published: July 2024

Background and Purpose

The gut hormone glucose‐dependent insulinotropic polypeptide (GIP) signals via the GIP receptor (GIPR), resulting in postprandial potentiation of glucose‐stimulated insulin secretion. The translation of results from rodent studies to human studies has been challenged by the unexpected effects of GIPR‐targeting compounds. We, therefore, investigated the variation between species, focusing on GIPR desensitization and the role of the receptor C‐terminus.

Experimental Approach

The GIPR from humans, mice, rats, pigs, dogs and cats was studied in vitro for cognate ligand affinity, G protein activation (cAMP accumulation), recruitment of beta‐arrestin and internalization. Variants of the mouse, rat and human GIPRs with swapped C‐terminal tails were studied in parallel.

Key Results

The human GIPR is more prone to internalization than rodent GIPRs. Despite similar agonist affinities and potencies for Gαs activation, especially, the mouse GIPR shows reduced receptor desensitization, internalization and beta‐arrestin recruitment. Using an enzyme‐stabilized, long‐acting GIP analogue, the species differences were even more pronounced. ‘Tail‐swapped’ human, rat and mouse GIPRs were all fully functional in their Gαs coupling, and the mouse GIPR regained internalization and beta‐arrestin 2 recruitment properties with the human tail. The human GIPR lost the ability to recruit beta‐arrestin 2 when its own C‐terminus was replaced by the rat or mouse tail.

Conclusions and Implications

Desensitization of the human GIPR is dependent on the C‐terminal tail. The species‐dependent functionality of the C‐terminal tail and the different species‐dependent internalization patterns, especially between human and mouse GIPRs, are important factors influencing the preclinical evaluation of GIPR‐targeting therapeutic compounds.
Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator
Authors: Huang Yuyou , Han Ziping , Shen Tong , Zheng Yangmin , Yang Zhenhong , Fan Junfen , Wang Rongliang , Yan Feng , Tao Zhen , Luo Yumin , Liu Ping
Published: July 2024

Aims

Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.

Methods

We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).

Results

rtPA increased neutrophil infiltration into the brain microvessels and worsened blood–brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.

Conclusion

Neutrophils play a crucial role in promoting ischemic injury and blood–brain barrier disruption, making them potential therapeutic targets.
Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion
Authors: Groba Marco Maria del Val , Saavedra Santana Pedro , Gonzalez del Castillo Luz Maria , Galvan Ruiz Mario , de Fernandez de Sanmamed Miguel , Urso Stefano , Guerra Hernández Elisabet , Quintana Paris Laura , Tout Castellano Michelle , Romero Lujan Jose Luis , Caballero Dorta Eduardo Jose , Guerra Dominguez Luisa Maria , Garcia Quintana Antonio
Published: July 2024

Background

We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy.

Methods

A retrospective, single‐center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality‐related events.

Results

Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity‐associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%–81.4%).

Conclusions

In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Upper gastrointestinal endoscopy in the surgically altered patient
Authors: Bhat Purnima , Kaffes Arthur John , Lassen Kristoffer , Aabakken Lars
Published: July 2024

As management of upper gastrointestinal malignancies improves, and with popularization of bariatric surgery, endoscopists are likely to meet patients with altered upper gastrointestinal anatomy. Short‐term, the surgery can cause complications like bleeding, leaks, and fistulas, and longer‐term problems such as intestinal or biliary anastomotic strictures or biliary stones can arise, all necessitating endoscopy. In addition, the usual upper gastrointestinal pathologies can also still occur. These patients pose unique challenges. To proceed, understanding the new layout of the upper gastrointestinal tract is essential. The endoscopist, armed with a clear plan for navigation, can readily diagnose and manage most commonly occurring conditions, such as marginal ulcers and proximal anastomotic strictures with standard endoscopic instruments. With complex reconstructions involving long segments of small bowel, such as Roux‐en‐Y gastric bypass, utilization of balloon‐assisted enteroscopy may be necessary, mandating modification of procedures such as endoscopic retrograde cholangiopancreatography. Successful endoscopic management of patients with altered anatomy will require prior planning and preparation to ensure the appropriate equipment, setting, and skill set is provided.
Probability ogives for trends in stock biomass and fishing mortality from landings time series
Authors: Roa‐Ureta Ruben H. , Amorim Patrícia , Segurado Susana
Published: July 2024

Most fisheries are conducted without any scientific knowledge about the size and productivity of the stocks that support them. This navigation in the dark in most fisheries is a major obstacle in making them sustainable sources of nutrition for people in general and income for fishers and other economic actors along supply chains. Fisheries that have not been assessed generally are data‐intermediate and data‐poor, the latter usually having annual time series of landings as the single piece of data available. A major effort in the last two decades has been directed toward developing ‘catch‐only’ stock assessment methods, although some of these methods have been tested and found deficient. Here we provide a novel approach to using annual landing time series as the single source of data to qualitatively judge the condition of un‐assessed stocks using frequentist cumulative probability ogives, both in terms of stock biomass and fishing mortality. A meta‐analysis of the FishSource database allowed us to infer statistical patterns from hundreds of assessed fisheries and thousands of annual landings, biomass, and fishing mortality observations. Four stock‐management types were considered separately in the analysis: short‐lived and others (mid‐ to long‐lived) stocks, controlled or not controlled by catch limits. Obtained cumulative probability ogives provide clear evaluations of stock biomass and fishing mortality trends in all four stock‐management types, leading to actionable information on probable current status and future trends. Using these probability ogives, we developed decision trees that lead to qualitative scores on the exploitation status of un‐assessed stocks.
Early Neolithic avifaunal remains from southeast Anatolia provide insight into Early Holocene species distributions and long‐term shifts in their range
Authors: Pöllath Nadja , Peters Joris
Published: July 2024

Based on the species‐rich avifaunas from Early Neolithic sites across Upper Mesopotamia (southeast Türkiye, northern Syria, northern Iraq), we compared seven species' Early Holocene distribution patterns with that of their modern species ranges. The avifaunal remains from four sites were analysed by the authors and bird identifications from 10 additional sites were extracted from published reports. In the case of the Common Crane Grus grus, Grey Partridge Perdix perdix and Black Francolin Francolinus francolinus, shifts in distributions relate to significant changes in climate marking the transition from the Pleistocene to the Holocene. In contrast, the massive decline of the Griffon Vulture Gyps fulvus represents a more recent phenomenon related to anthropogenic impact on their habitats and food sources. For the Black‐bellied Sandgrouse Pterocles orientalis and the Pin‐tailed Sandgrouse P. alchata, changes in distributional range from the Early Holocene to the present could not be detected. Finally, a single bone of Macqueen's Bustard Chlamydotis macqueenii at Göbekli Tepe is unexpected and conceivably we are dealing with the remains of a rare vagrant, more likely to be found in dry steppe and desert habitats, which were located south of the study area at that time. This study highlights the value of archaeozoological finds in helping to understand how species distributional ranges have changed over time. Similarly, our work suggests that authors studying archaeozoological data should not assume that present‐day distributional ranges of taxa of interest represent the ranges of these species in the past.
Associations of E‐proteinoid 3 receptor genetic polymorphisms with salt sensitivity, longitudinal blood pressure changes, and hypertension incidence in Chinese adults
Authors: Chang Ming‐Ke , Wu Guan‐Ji , Bao Peng , Yao Shi , Du Ming‐Fei , Chu Chao , Wang Dan , Jia Hao , Sun Yue , Yan Yu , Zhang Xi , Hu Gui‐Lin , Man Zi‐Yue , Guo Tong‐Shuai , Luo Wen‐Jing , Li Hao , Wang Yang , Mu Jian‐Jun
Published: July 2024

The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.
Prenatal diagnosis of the umbilical cord torsion at the placental cord insertion site: A case report and literature review
Authors: Hashiramoto Shin , Arakaki Tatsuya , Takita Hiroko , Kaneko Mayumi , Matsuoka Ryu , Sekizawa Akihiko
Published: July 2024

A 35‐year‐old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the “Sunset Sign,” an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.
Attitude and experience of obstetricians and gynecologists toward eating disorders assessment and management in Japan: A nationwide survey
Authors: Ogawa Mariko , Komura Hiroko , Ono Yoko , Nose‐Ogura Sayaka , Kawai Keisuke , Terauchi Masakazu ,   from the subcommittee “Survey of the Obstetrics and Gynecology‐Based Treatment for Patients with Eating Disorders in Japan” in Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2021–2022
Published: July 2024

Aim

To investigate the attitudes and experiences of obstetricians and gynecologists in treating women with eating disorders (EDs) in Japan.

Methods

Members of the Japan Society of Obstetrics and Gynecology were invited to participate in a web‐based survey from March 1 to 31, 2022. We asked about the attitudes of obstetricians and gynecologists toward women with weight loss‐related amenorrhea and their experiences in treating EDs. We also assessed the characteristics of physicians who see many ED patients.

Results

A total of 662 ob/gyns. responded to the survey. While treating weight loss‐related amenorrhea, 25.8% reported screening patients for EDs. 88.5% of respondents reported having treated ED patients. The main medical concerns described when treating pregnant women with ED were fetal growth restriction and preterm delivery. The most common type of ED encountered by participants in both perinatal and infertility care settings was anorexia nervosa. Characteristics of physicians who treated 10 or more EDs per year were being board certified in women's health care and not providing delivery services (OR = 4.809, 1.896). The most common comment regarding optimizing the management of patients with EDs in obstetrics and gynecology practice was the need to implement guidelines for ED management.

Conclusions

Many obstetricians and gynecologists in Japan treat patients with ED. Standardized guidelines for the management of EDs for obstetricians and gynecologists are needed.
The structure of bacteria–fungi bipartite networks along elevational gradients in contrasting climates
Authors: Zhao Wenqian , Soininen Janne , Hu Ang , Liu Jinfu , Li Mingjia , Wang Jianjun
Published: July 2024

Climate change is altering species distribution and modifying interactions in microbial communities. Understanding microbial community structure and their interactions is crucial to interpreting ecosystem responses to climate change. Here, we examined the assemblages of stream bacteria and fungi, and the associations between the two groups along elevational gradients in two regions with contrasting precipitation and temperature, that is the Galong and Qilian mountains of the Tibetan Plateau. In the wetter and warmer region, the species richness significantly increased and decreased with elevation for bacteria and fungi, respectively, while were nonsignificant in the drier and colder region. Their bipartite network structure was also different by showing significant increases in connectance and nestedness towards higher elevations only in the wetter and warmer region. In addition, these correlation network structure generally exhibited similar positive association with species richness in the wetter and warmer region and the drier and colder region. In the wetter and warmer region, climatic change along elevation was more important in determining connectance and nestedness, whereas microbial species richness exerted a stronger influence on network structure and robustness in the drier and colder region. These findings indicate substantial forthcoming changes in microbial diversity and network structure in warming climates, especially in wetter and warmer regions on Earth, advancing the understanding of microbial bipartite interactions' response to climate change.
Fluid‐Dynamic Modeling of Flow in Embryonic Tissue Indicates That Lymphatic Valve Location Is Not Consistently Determined by the Local Fluid Shear or Its Gradient
Authors: Bertram Christopher D. , Macaskill Charlie
Published: July 2024

Objective

Intravascular lymphatic valves often occur in proximity to vessel junctions. It is commonly held that disturbed flow at junctions is responsible for accumulation of valve‐forming cells (VFCs) at these locations as the initial step in valve creation, and the one which explains the association with these sites. However, evidence in favor is largely limited to cell culture experiments.

Methods

We acquired images of embryonic lymphatic vascular networks from day E16.5, when VFC accumulation has started but the developing valve has not yet altered the local vessel geometry, stained for Prox1, which co‐localizes with Foxc2. Using finite‐element computational fluid mechanics, we simulated the flow through the networks, under conditions appropriate to this early development stage. Then we correlated the Prox1 distributions with the distributions of simulated fluid shear and shear stress gradient.

Results

Across a total of 16 image sets, no consistent correlation was found between Prox1 distribution and the local magnitude of fluid shear, or its positive or negative gradient.

Conclusions

This, the first direct semi‐empirical test of the localization hypothesis to interrogate the tissue from in vivo at the critical moment of development, does not support the idea that a feature of the local flow determines valve localization.
Arithmetical pluralism and the objectivity of syntax
Authors: Picollo Lavinia , Waxman Daniel
Published: July 2024

Arithmetical pluralism is the view that there is not one true arithmetic but rather many apparently conflicting arithmetical theories, each true in its own language. While pluralism has recently attracted considerable interest, it has also faced significant criticism. One powerful objection, which can be extracted from Parsons (2008), appeals to a categoricity result to argue against the possibility of seemingly conflicting true arithmetics. Another salient objection raised by Putnam (1994) and Koellner (2009) draws upon the arithmetization of syntax to argue that arithmetical pluralism is inconsistent with the objectivity of syntax. First, we review these arguments and explain why they ultimately fail. We then offer a novel, more sophisticated argument that avoids the pitfalls of both. Our argument combines strategies from both objections to show that pluralism about arithmetic entails pluralism about syntax. Finally, we explore the viability of pluralism in light of our argument and conclude that a stable pluralist position is coherent. This position allows for the possibility of rival packages of arithmetic and syntax theories, provided that they systematically co‐vary with one another.
ArabidopsisPROTODERMAL FACTOR2 binds lysophosphatidylcholines and transcriptionally regulates phospholipid metabolism
Authors: Wojciechowska Izabela , Mukherjee Thiya , Knox‐Brown Patrick , Hu Xueyun , Khosla Aashima , Subedi Bibek , Ahmad Bilal , Mathews Graham L. , Panagakis Ashley A. , Thompson Kyle A. , Peery Sophie T. , Szlachetko Jagoda , Thalhammer Anja , Hincha Dirk K. , Skirycz Aleksandra , Schrick Kathrin
Published: July 2024

Plant homeodomain leucine zipper IV (HD‐Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)‐related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear.

Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START‐dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding.

We additionally found that PDF2 acts as a transcriptional regulator of phospholipid‐ and phosphate (Pi) starvation‐related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity.

We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.
Identification of schizophrenia by applying interpretable radiomics modeling with structural magnetic resonance imaging of the cerebellum
Authors: Bang Minji , Park Kisung , Choi Seoung‐Ho , Ahn Sung Soo , Kim Jinna , Lee Seung‐Koo , Park Yae Won , Lee Sang‐Hyuk
Published: July 2024

Aims

The cerebellum is involved in higher‐order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1‐weighted magnetic resonance imaging (T1‐MRI) of the cerebellum.

Methods

A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1‐MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability.

Results

We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82–0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second‐order size zone non‐uniformity feature from the right lobule IX and first‐order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia.

Conclusion

The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease‐defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker‐based decision‐making in clinical practice.
Radiographic assessment of the peri‐implant site
Authors: Sahrmann Philipp , Kühl Sebastian , Dagassan‐Berndt Dorothea , Bornstein Michael M. , Zitzmann Nicola U.
Published: July 2024

While peri‐implant mucositis relies solely on clinical parameters, radiological assessment becomes indispensable for diagnosing peri‐implantitis. Intraoral radiography, with its simplicity of application, low radiation exposure, and adequate representation of peri‐implant structures, stands out as the standard of care for both immediate and follow‐up assessments. Standardization by custom‐made radiologic splints allows for excellent comparability with previous images and allows for the determination of even small changes in contour and density of the peri‐implant bone. Furthermore, other radiographic modalities like panoramic radiography and cone beam computed tomography (CBCT) may provide useful features for specific patients and clinical cases while also showing innate limitations. Beyond the assessment of the marginal peri‐implant bone level as the crucial parameter of clinical relevance, radiologic assessment may reveal various other findings related to the prosthetic restoration itself, the precision of its fit to the implant, and the peri‐implant soft and hard tissues. Since such findings can be crucial for the assessment of peri‐implant health and the implants' prognosis, a systematic diagnostic evaluation pathway for a thorough assessment is recommended to extract all relevant information from radiologic imaging. This article also provides an overview of the clinical and chronological indications for different imaging modalities in peri‐implant issues.
External skeletal fixation for the treatment of pelvic fractures in cats
Authors: Fitzpatrick Noel , Guthrie James W. , Hamilton Michael H.
Published: July 2024

Objective

To report the technique and the outcome for the repair of pelvic fractures in cats using external skeletal fixation (ESF).

Study design

Retrospective case series.

Animals

Client‐owned cats (n = 125).

Methods

Medical records of cats with pelvic fractures, treated with an ESF between June 2001 and June 2009, were reviewed. Preoperative, immediate postoperative, and more than 4 weeks’ postoperative radiographs were compared. Clinical examination was performed 4 to 9 weeks following surgery. Longer term follow up (4 to 80 months) was conducted by client questionnaire.

Results

No intraoperative complications occurred. There was no change in the pelvic canal width observed on follow‐up radiographs (p = .16). Implant loosening was noted on follow‐up radiographs in 16/125 (13%) of cases, and 67/803 (8%) pins were palpably loose at the time of frame removal. The mean time to frame removal was 37 ± 9 days. No long‐term complications were reported. Long‐term mean mobility score was 95 ± 5 and median lameness was 0 (range: 0–2).

Conclusion

An ESF may be successfully applied for the stabilization of various pelvic fractures in cats.

Clinical significance

The application of an ESF for the management of pelvic fractures in cats provides good outcomes.
Leveraging biotin-based proximity labeling to identify cellular factors governing early alphaherpesvirus infection
Authors: Quan Jenai , Fan Qing , Simons Lacy M. , Smukowski Samuel N. , Pegg Caitlin , Longnecker Richard , Savas Jeffrey N. , Hultquist Judd F. , Smith Gregory A.
Published: July 2024

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 and pseudorabies virus, establish a lifelong presence within the peripheral nervous system of their mammalian hosts. Upon entering cells, two conserved tegument proteins, pUL36 and pUL37, traffic DNA-containing capsids to nuclei. These proteins support long-distance retrograde axonal transport and invasion of the nervous system
in vivo
. To better understand how pUL36 and pUL37 function, recombinant viral particles carrying BioID2 fused to these proteins were produced to biotinylate cellular proteins in their proximity (<10 nm) during infection. Eighty-six high-confidence host proteins were identified by mass spectrometry and subsequently targeted by CRISPR-Cas9 gene editing to assess their contributions to early infection. Proteins were identified that both supported and antagonized infection in immortalized human epithelial cells. The latter included zyxin, a protein that localizes to focal adhesions and regulates actin cytoskeletal dynamics. Zyxin knockout cells were hyper-permissive to infection and could be rescued with even modest expression of GFP-zyxin. These results provide a resource for studies of the virus-cell interface and identify zyxin as a novel deterrent to alphaherpesvirus infection.

IMPORTANCE

Neuroinvasive alphaherpesviruses are highly prevalent with many members found across mammals [e.g., herpes simplex virus type 1 (HSV-1) in humans and pseudorabies virus in pigs]. HSV-1 causes a range of clinical manifestations from cold sores to blindness and encephalitis. There are no vaccines or curative therapies available for HSV-1. A fundamental feature of these viruses is their establishment of lifelong infection of the nervous system in their respective hosts. This outcome is possible due to a potent neuroinvasive property that is coordinated by two proteins: pUL36 and pUL37. In this study, we explore the cellular protein network in proximity to pUL36 and pUL37 during infection and examine the impact of knocking down the expression of these proteins upon infection.
Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway
Authors: Li Ying-Jie , Li Jing , Dai Cong
Published: July 2024

Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium
sensu stricto
1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell
in vitro
. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.

IMPORTANCE

Irritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this
in vitro
and
in vivo
assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells
in vivo
and
in vitro
by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium
sensu stricto
1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.
Variations in candidalysin amino acid sequence influence toxicity and host responses
Authors: Wickramasinghe Don N. , Lyon Claire M. , Lee Sejeong , Hepworth Olivia W. , Priest Emily L. , Maufrais Corinne , Ryan Adam P. , Permal Emmanuelle , Sullivan Derek , McManus Brenda A. , Hube Bernhard , Butler Geraldine , d'Enfert Christophe , Naglik Julian R. , Richardson Jonathan P.
Published: July 2024

Candida albicans
causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in
C. albicans
strain SC5314, but recent investigations have revealed candidalysin “variants” of differing amino acid sequence in isolates of
C. albicans
, and the related species
C. dubliniensis
, and
C tropicalis
, suggesting that sequence variation among candidalysins may be widespread in natural populations of these
Candida
species. Here, we analyzed
ECE1
gene sequences from 182
C
.
albicans
isolates, 10
C
.
dubliniensis
isolates, and 78
C
.
tropicalis
isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant
Candida
species.

IMPORTANCE

Fungal infections are a significant burden to health. Candidalysin is a toxin produced by
Candida albicans
that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species
C. dubliniensis
and
C. tropicalis
, thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin “variant” toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of
C. albicans
,
C. dubliniensis
, and
C. tropicalis
and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.
Genome sequences of three
Bartonella schoenbuchensis
strains from Czechia
Authors: Solis Cayo Luis , Hammerbauerová Iva , Sommer Julian , Nemati Zahra , Ballhorn Wibke , Tsukayama Pablo , Dichter Alexander , Votýpka Jan , Kempf Volkhard A. J.
Published: July 2024

Bartonella schoenbuchensis
causes bacteremia in ruminants and is transmitted by deer keds. Here, we report the complete genome sequences of three
B. schoenbuchensis strains
(L2, L19, and L24) recently isolated from deer keds (
Lipoptena fortisetosa
) in Czechia.
Hospital mortality and length of stay associated with
Enterobacterales
positive blood cultures: a multicenter analysis
Authors: Cooper Lauren , Yu Kalvin , Van Benten Kayla , Patkar Anuprita , Ye Gang , Gregory Sara , Ai ChinEn , Gupta Vikas
Published: July 2024

Delayed time to antimicrobial susceptibility results can impact patients’ outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by
Enterobacterales
(ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98);
P
< 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90);
P
= 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (
P
< 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57–65 h and >65 h (
P
= 0.005 and
P
< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.

IMPORTANCE

For patients diagnosed with bloodstream infections (BSI) caused by
Enterobacterales
(ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.
Supplemental Material: Upper Paleozoic komatiites near Mashhad, NE Iran
Authors: Mobasheri Mohsen , al. et
Published: July 2024

 S1—a description of the contents of an article in preparation; S2—analytical methods; Table S1—compositions of olivine; Table S2—compositions of Cr spinel; Table S3—major and trace elements in samples; and Figures S1–S5.
Pseudomonas and aspergillus symbiotic coinfections in a case of chronic obstructive pulmonary disease and diabetes mellitus
Authors: Das Drupad , Panda Prasan Kumar
Published: July 2024

Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections withPseudomonas aeruginosaandAspergillus fumigatus, respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.
Aggressive hydration with lactated Ringer’s solution versus plasma solution for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (ALPS study): protocol for a multicentre, double-blind, randomised controlled trial
Authors: Cho In Rae , Choi Jin Ho , Park Joo Kyung , Huh Gunn , Lee Sang Hyub , Paik Woo Hyun , Park Do Hyun
Published: July 2024

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer’s solution versus plasma solution in preventing PEP.

Method and analysis

This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer’s solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms.

Ethics and dissemination

Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences.

Trial registration number

NCT05832047.

Protocol version

Ver 4.1 (2023).
Anxiety and resilience in palliative medicine physicians
Authors: Velásquez Marín Cristhian Alexis , Avendaño-Vásquez Carlos Javier
Published: July 2024

Objective

To identify the relationship between the degree of anxiety and the capacity for resilience in palliative care physicians.

Methods

Cross-sectional analytical study with non-probability sampling. We included 42 Colombian Palliative Care Physicians and administered a sociodemographic questionnaire, the Zung Anxiety Scale and the Resilience Scale.

Results

42 palliative care physicians with an average age of 41 participated in the study. Anxious symptoms were present in 100% of the physicians evaluated. Mild or moderate anxiety was identified in 93.7% of the population and 6.3% of people with severe anxiety symptoms. Less than half of the participants considered demonstrated high levels of resilience. We found an inverse and significant correlation between the factors that make up the Resilience Scale and the manifestation of psychological and physical symptoms of anxiety.

Conclusion

Our results reflect that the population of palliative care physicians has a higher risk and exposure to developing anxiety and its adverse outcomes. We found higher anxiety levels compared with other studies so this population requires greater vigilance and intervention in treating and preventing mental health difficulties.
Zero-Knowledge Proofs and Their Role within the Blockchain
Authors: Williams Alex
Published: July 2024

In each issue of
Communications
, we publish selected posts or excerpts from the many blogs on our website. The views expressed by bloggers are their own and not necessarily held by
Communications
or the Association for Computing Machinery.

Read more blogs and join the discussion at https://cacm.acm.org/blog.

https://cacm.acm.org/blog

An examination of the intricate world of zero-knowledge proofs and how they may be used to enhance blockchain security and privacy.
Age Verification Systems Will Be a Personal Identifiable Information Nightmare
Authors: Scheffler Sarah
Published: July 2024

Online ID checking is insecure, bad for privacy, and will not help children.
Working Models for Tackling Tech Debt
Authors: Matsudaira Kate
Published: July 2024

Remember that not all debt is bad, and sometimes, in fact, strategic tech debt can even be used as a valuable tool to achieve certain business goals?just as financial debt can be taken on to obtain capital that can be invested in other profitable ventures. For example, taking a shortcut to get a product to market quickly could prove to be a wise decision if it allows the company to learn from customer feedback and then iterate accordingly on the product. But like barnacles on a ship, too much tech debt can slow you down, so be vigilant about managing it.
Feeding the Body Through the Skin: Ethosomes and Transethosomes as a New Topical Delivery System for Bioactive Compounds
Authors: Esposito Elisabetta , Pecorelli Alessandra , Ferrara Francesca , Lila Mary Ann , Valacchi Giuseppe
Published: July 2024

Because the feeding of our body through the oral route can be associated with many drawbacks due to the degradation of natural molecules during transit in the gastrointestinal tract, a transdermal delivery strategy, usually employed in the pharmaceutical field, can present an effective alternative for delivery of bioactives and nutrients from foods. In this review, the chance to feed the body with nutritive and bioactive molecules from food through transdermal administration is discussed. Various nanotechnological devices employed for topical and transdermal delivery of bioactive compounds are described. In addition, mechanisms underlying their potential use in the delivery of nutritive molecules, as well as their capability to efficaciously reach the dermis and promote systemic distribution, are detailed.