bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia
Authors: Mustafá Emilio R. , Gambeta Eder , Stringer Robin N. , Souza Ivana A. , Zamponi Gerald W. , Weiss Norbert 
Published: November 2022

AbstractTrigeminal neuralgia (TN) is a rare form of chronic neuropathic pain characterized by spontaneous or elicited paroxysms of electric shock-like or stabbing pain in a region of the face. While most cases occur in a sporadic manner and are accompanied by intracranial vascular compression of the trigeminal nerve root, alteration of ion channels has emerged as a potential exacerbating factor. Recently, whole exome sequencing analysis of familial TN patients identified 19 rare variants in the gene CACNA1H encoding for Cav3.2T-type calcium channels. An initial analysis of 4 of these variants pointed to a pathogenic role. In this study, we assessed the electrophysiological properties of 13 additional TN-associated Cav3.2 variants expressed in tsA-201 cells. Our data indicate that 6 out of the 13 variants analyzed display alteration of their gating properties as evidenced by a hyperpolarizing shift of their voltage dependence of activation and/or inactivation resulting in an enhanced window current supported by Cav3.2 channels. An additional variant enhanced the recovery from inactivation. Simulation of neuronal electrical membrane potential using a computational model of reticular thalamic neuron suggests that TN-associated Cav3.2 variants could enhance neuronal excitability. Altogether, the present study adds to the notion that ion channel polymorphisms could contribute to the etiology of some cases of TN and further support a role for Cav3.2 channels.
Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma
Authors: Lucarini Valeria , Melaiu Ombretta , D’Amico Silvia , Pastorino Fabio , Tempora Patrizia , Scarsella Marco , Pezzullo Marco , De Ninno Adele , D’Oria Valentina , Cilli Michele , Emionite Laura , Infante Paola , Di Marcotullio Lucia , De Ioris Maria Antonietta , Barillari Giovanni , Alaggio Rita , Businaro Luca , Ponzoni Mirco , Locatelli Franco , Fruci Doriana 
Published: November 2022

Abstract
Background
Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitize poorly T-cell-infiltrated neuroblastoma (NB) to the host antitumor immune response.

Methods
975A2 and 9464D NB cell lines derived from spontaneous tumors of TH-MYCN transgenic mice were employed to study drug combinations able of enhancing the antitumor immune response using in vivo and ex vivo approaches. Migration of immune cells towards drug-treated murine-derived organotypic tumor spheroids (MDOTS) were assessed by microfluidic devices. Activation status of immune cells co-cultured with drug-treated MDOTS was evaluated by flow cytometry analysis. The effect of drug treatment on the immune content of subcutaneous or orthotopic tumors was comprehensively analyzed by flow-cytometry, immunohistochemistry and multiplex immunofluorescence. The chemokine array assay was used to detect soluble factors released into the tumor microenvironment. Patient-derived organotypic tumor spheroids (PDOTS) were generated from human NB specimens. Migration and activation status of autologous immune cells to drug-treated PDOTS were performed.

Results
We found that treatment with low-doses of mitoxantrone (MTX) recalled immune cells and promoted CD8+ T and NK cell activation in MDOTS when combined with TGFβ and PD-1 blockade. This combined immunotherapy strategy curbed NB growth resulting in the enrichment of a variety of both lymphoid and myeloid immune cells, especially intratumoral dendritic cells (DC) and IFNγ- and granzyme B-expressing CD8+ T cells and NK cells. A concomitant production of inflammatory chemokines involved in remodelling the tumor immune landscape was also detected. Interestingly, this treatment induced immune cell recruitment against PDOTS and activation of CD8+ T cells and NK cells.

Conclusions
Combined treatment with low-dose of MTX and anti-TGFβ treatment with PD-1 blockade improves antitumor immunity by remodelling the tumor immune landscape and overcoming the immunosuppressive microenvironment of aggressive NB.
The role of social, demographic and territorial factors in the late detection of hip dysplasia in children in the Republic of Kazakhstan
Authors: Tastanbekova Zhanna , Karabekova Roza , Lozovoy Vassiliy , Angelov Aleksandr , Suleimenov Zhomart , Khuzhakhmedova Rimma 
Published: November 2022

Abstract
Background
The aim of this research is to identify and study the role of social, demographic and territorial factors in the late detection of children with hip dysplasia.

Methods
We conducted a retrospective cohort study of epidemiological data of patients treated in a hospital in the department of orthopedics of the unitary enterprise based on the right of "Multidisciplinary children's municipal hospital No.2" Nur-Sultan (Kazakhstan) in the period from September 2019 to February 2021. The analysis of archival case histories of 309 patients was carried out. There were 214 early and 95 late detections of this disease. Late detection of hip dysplasia was significantly more likely at birth in cranial presentation (81%, p <0.004).

Results
Two-dimensional analysis also showed that late detection was more likely in patients from rural areas (228 children, 73.8%, p < 0.001), and that (26 children, 11.4%, p = 0.005) these were children from regions with lower income (42500 tenge per month, p<0.001). There were also significant differences (p = 0.015) in the early (214 children, 69.26%) and late (95 children, 30.7%) diagnosis of hip dysplasia among children whose parents used a national cradle with tight swaddling (95% CI: 1.16 – 4.49).

Conclusions
In our study, we found that children from rural regions of the Republic of Kazakhstan, indigenous Kazakh nationality, using the national cradle in their everyday life, as well as from regions with low average incomes, were significantly more likely to be exposed to late detection of hip dysplasia.
Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial
Authors: Heming Nicholas , Carlier Robert , Prigent Helene , Mekki Ahmed , Jousset Camille , Lofaso Frederic , Ambrosi Xavier , Bounab Rania , Maxime Virginie , Mansart Arnaud , Crenn Pascal , Moine Pierre , Foltzer Fabien , Cuenoud Bernard , Konz Tobias , Corthesy John , Beaumont Maurice , Hartweg Mickaël , Roessle Claudia , Preiser Jean-Charles , Breuillé Denis , Annane Djillali 
Published: November 2022

Abstract
Background
A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss.

Methods
This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome. Patients received a specific combination of five amino acids or placebo mixed with enteral feeding for 21 days. Markers of renal function, gut barrier structure and functionality were collected at baseline and 1, 2, 3 and 8 weeks after randomization. Muscle structure and function were assessed through MRI measurements of the anterior quadriceps volume and by twitch airway pressure. Data were compared between groups relative to the baseline.

Results
Thirty-five critically ill patients were randomized. The amino acid blend did not impair urine output, blood creatinine levels or creatinine clearance. Plasma citrulline levels increased significantly along the treatment period in the amino acid group (difference in means [95% CI] 5.86 [1.72; 10.00] nmol/mL P = 0.007). Alanine aminotransferase and alkaline phosphatase concentrations were lower in the amino acid group than in the placebo group at one week (ratio of means 0.5 [0.29; 0.86] (P = 0.015) and 0.73 [0.57; 0.94] (P = 0.015), respectively). Twitch airway pressure and volume of the anterior quadriceps were greater in the amino acid group than in the placebo group 3 weeks after randomization (difference in means 10.6 [0.99; 20.20] cmH20 (P = 0.035) and 3.12 [0.5; 5.73] cm3/kg (P = 0.022), respectively).

Conclusions
Amino acid supplementation increased plasma citrulline levels, reduced alanine aminotransferase and alkaline phosphatase levels, and improved twitch airway pressure and anterior quadriceps volume.
Trial registration ClinicalTrials.gov, NCT02968836. Registered November 21, 2016.
N6-methyladenosine-mediated SH3BP5-AS1 upregulation promotes GEM chemoresistance in pancreatic cancer by activating the Wnt signaling pathway
Authors: Lin Chengjie , Wang Yan , Dong Yihong , Lai Shihui , Wang Liang , Weng Shangeng , Zhang Xiang 
Published: November 2022

Abstract
Background
Pancreatic cancer (PC) is highly malignant. Chemotherapy is the main treatment strategy, especially for patients with advanced PC. However, chemoresistance has always been a frequently encountered bottleneck. Hence, there is an urgent need to enhance the sensitivity of PC to gemcitabine (GEM).

Results
We demonstrated that SH3BP5-AS1 was significantly upregulated in GEM-resistant PC and predicted a poorer prognosis. SH3BP5-AS1 stability was regulated by ALKBH5/IGF2BP1-mediated m6A modification. Loss of SH3BP5-AS1 reduced PC cell migration and invasion and enhanced the sensitivity of PC to GEM, as confirmed by gain- and loss-of-function assays in vitro and in vivo. Bioinformatics analysis revealed that SH3BP5-AS1 acted as a ceRNA against miR-139-5p and directly targeted CTBP1, affecting the biological behavior of PC cells. The mechanistic studies revealed that the upregulation of SH3BP5-AS1 increased CTBP1 expression by directly activating the Wnt signaling pathway, promoting GEM resistance.

Conclusions
This study revealed that SH3BP5-AS1 activated Wnt signaling pathway by sponging miR-139-5p, upregulating CTBP1 expression, and contributing to the sensitivity of PC cells to GEM. SH3BP5-AS1 might be a potential target for PC therapy.
Effect of personalized perioperative blood pressure management on postoperative complications and mortality in high-risk patients having major abdominal surgery: protocol for a multicenter randomized trial (IMPROVE-multi)
Authors: Bergholz Alina , Meidert Agnes S. , Flick Moritz , Krause Linda , Vettorazzi Eik , Zapf Antonia , Brunkhorst Frank M. , Meybohm Patrick , Zacharowski Kai , Zarbock Alexander , Sessler Daniel I. , Kouz Karim , Saugel Bernd 
Published: November 2022

Abstract
Background
Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management—based on preoperative automated blood pressure monitoring—reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery.

Methods
IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery.

Discussion
Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery.

Trial registration
ClinicalTrials.gov NCT05416944. Registered on June 14, 2022.
Effect of comprehensive geriatric assessment for frail elderly patients operated for colorectal cancer—the colorectal cancer frailty study: study protocol for a randomized, controlled, multicentre trial
Authors: Normann Maria , Ekerstad Niklas , Angenete Eva , Prytz Mattias 
Published: November 2022

AbstractBackgroundColorectal cancer (CRC) is the third most common cancer worldwide, with a median age of 72–75 years at diagnosis. Curative treatment usually involves surgery; if left untreated, symptoms may require emergency surgery. Therefore, most patients will be accepted for surgery, despite of high age or comorbidity. It is known that elderly patients suffer higher risks after surgery than younger patients, in terms of complications and mortality. Assessing frailty and offering frail elderly patients individualized treatment according to the comprehensive geriatric assessment (CGA) and care concept has been shown to improve the outcome for frail elderly patients in other clinical contexts.MethodsThis randomized controlled multicentre trial aims to investigate if CGA and care prior to curatively intended surgery for CRC in frail elderly patients will improve postoperative outcome. All patients ≥ 70 years with surgically curable CRC will be screened for frailty using the Clinical Frailty Scale (CFS-9). Frail patients will be offered inclusion. Randomization is stratified for colon or rectal cancer. Patients in the intervention group are, in addition to standard protocol, treated according to CGA and care. This consists of individualized assessments and interventions, established by a multiprofessional team. Patients in the control group are treated according to best known practice as stipulated by Swedish colorectal cancer treatment guidelines, within an enhanced recovery after surgery (ERAS) setting. The primary outcome is 90-day mortality. Secondary outcomes are the length of hospital stay and total number of hospital days within 3 months, discharge destination, 30-day readmission, ADL, safe medication assessment, CFS-9 score, complications, Health-Related Quality of Life (HRQoL) at 2-month follow-up in comparison to baseline measurements, health economical calculations including cost-effectiveness analysis based on costs of hospital care and primary care, mortality and HRQoL at baseline, 2- and 12-month follow-up and all-cause 1-year mortality.DiscussionThe trial is the first of its size and extent to investigate intervention with CGA and care prior to surgery for CRC in frail elderly patients. If this addition proves to be favourable, it could have implications on future care of frail elderly patients with CRC.Trial registrationClinicalTrials.govNCT04358328. Registered on 4 February 2020
Modulation of the porcine intestinal microbiota in the course of Ascaris suum infection
Authors: Springer Andrea , Wagner Liane , Koehler Sarina , Klinger Stefanie , Breves Gerhard , Brüggemann Dagmar A. , Strube Christina 
Published: November 2022

Abstract
Background
The porcine roundworm Ascaris suum impairs feed conversion and weight gain, but its effects on intestinal microbiota remain largely unexplored.

Methods
Modulation of the intestinal microbiota was assessed in pigs that were infected once with 10,000 A. suum eggs and pigs that received a trickle infection (1000 eggs/day over 10 days), compared with a non-infected control group. Six pigs each were sacrificed per group at days 21, 35 and 49 post-infection (p.i.). Faecal samples taken weekly until slaughter and ingesta samples from different intestinal compartments were subjected to next-generation sequencing of the bacterial 16S rRNA gene.

Results
The results revealed marked differences between the single- and the trickle-infected group. Single infection caused a remarkable but transient decrease in microbial diversity in the caecum, which was not observed in the trickle-infected group. However, an increase in short-chain fatty acid-producing genera in the caecum on day 21 p.i., which shifted to a decrease on day 35 p.i., was common to both groups, possibly related to changes in excretory–secretory products following the parasite’s final moult. Faecal microbial interaction networks were more similar between the single-infected and control group than the trickle-infected group. In addition, a lower degree of similarity over time indicated that A. suum trickle infection prevented microbiota stabilization.

Conclusions
These different patterns may have important implications regarding the comparability of experimental infections with natural scenarios characterized by continuous exposure, and should be confirmed by further studies.

Graphical Abstract
Aerococcus urinae, a rare cause of aortic root abscess: a case report
Authors: Tiong Chong Wei , Bartolo Caroline , Walton Aaron , Athan Eugene 
Published: November 2022

Abstract
Background
Aerococcus urinae is a bacterium of emerging clinical interest that most commonly causes urinary tract infections (UTI) but can also result in invasive infections. It is a catalase-negative, alpha-haemolytic gram-positive coccus that grows in clusters or tetrads and usually causes urinary tract infections. While rare, infective endocarditis must be considered when A. urinae is isolated in blood culture. The mortality rate of A. urinae infective endocarditis is similar to overall endocarditis mortality. We report a rare case of aortic root abscess caused by A. urinae.

Case presentation
An 82-year-old Caucasian man presented to hospital with behavioural change and severe malnutrition and was managed for psychotic depression. On day 34 of his inpatient stay, a febrile episode prompted blood cultures, which grew Aerococcus. urinae. Investigations revealed a bicuspid aortic valve, aortic valve endocarditis and aortic root abscess. He also had prostatomegaly. He underwent aortic valve replacement, received 6 weeks of intravenous ceftriaxone and recovered.

Conclusion
Infective endocarditis should be considered in patients with persistent Aerococcus urinae bacteraemia. Accurate identification with mass spectrometry is recommended to avoid misidentification as staphylococcus, streptococcus or enterococcus, which is a possibility with conventional laboratory methods.
Acute respiratory distress syndrome following administration of gadolinium contrast agent: a case report
Authors: Osawa Eduardo Atsushi , Kleiman Juliana Fernandez Fernandes , Maciel Alexandre Toledo 
Published: November 2022

Abstract
Background
Gadolinium-based contrast agents are used extensively in magnetic resonance imaging to assist diagnosis of medical conditions. Despite their documented safety profile, severe adverse events do occur, and their documentation may serve to raise the awareness of the medical community.

Case presentation
We report the case of a 15-year-old white Latin American female patient admitted to the intensive care unit for acute respiratory distress syndrome following administration of gadolinium. She did not have rash or tongue swelling but developed hypotension responsive to fluid administration and severe hypoxemia. Chest computed tomography revealed bilateral pulmonary compromise with multiple confluent consolidations. She received methylprednisolone and noninvasive ventilatory support including bilevel positive airway pressure ventilation and high-flow nasal cannula, and underwent a rapid recovery.

Conclusion
Gadolinium-based contrast agent-induced acute respiratory distress syndrome, albeit rare, should be included in the differential diagnosis of respiratory failure shortly after magnetic resonance imaging, which is nowadays a frequent diagnostic procedure, potentially increasing the awareness of this serious complication.
A novel fault location method for distribution networks with distributed generations based on the time matrix of traveling-waves
Authors: Cheng Liang , Wang Tao , Wang Yi 
Published: November 2022

AbstractTo improve location speed, accuracy and reliability, this paper proposes a fault location method for distribution networks based on the time matrix of fault traveling waves. First, an inherent time matrix is established according to the normalized topology of the target distribution network, and a post-fault time matrix is obtained by extracting the head data of initial waves from traveling wave detection devices. A time determination matrix is then obtained using the difference operation between the two matrices. The features of the time determination matrix are used for fault section identification and fault distance calculation, to accurately locate faults. The method is modified by considering economic benefits, through the optimal configuration of detection devices of traveling waves when calculating fault distances. Simulation results show that the proposed method has good adaptation with higher fault location accuracy than two other typical ones. It can deal with faults on invalid branches, and the error rate is under 0.5% even with connected DGs.
Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV
Authors: Friebel-Klingner Tara M. , Bazzett-Matabele Lisa , Ramogola-Masire Doreen , Monare Barati , Ralefala Tlotlo B. , Seiphetlheng Alexander , Ramontshonyana Gaobakwe , Vuylsteke Peter , Mitra Nandita , Wiebe Douglas J. , Rebbeck Timothy R. , McCarthy Anne Marie , Grover Surbhi 
Published: November 2022

PURPOSE Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.