bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of comparing between auditory manifestations in post-COVID 2019 and 2023
Authors: Abd El Hady Heba Tallah sherif , Kolkaila Enaas Ahmad 
Published: November 2024

Abstract
Background
It’s known that COVID-19 affects the audio-vestibular system, while its variant is not studied yet. Accordingly, this work was designed to study the effect of COVID-19 and its variant on audio-vestibular system and to compare between symptoms and effects of these two.

Methods
A case- control study was conducted, with each case and control group consisting of 75 people who were age and gender matched. Their age ranged from 18 to 45 years. They were splited into three groups as follows: Study group 1 (post-COVID-19), it consisted of 25 post recovery adults, Study group 2 (post- COVID-23) consisted of 25 post recovery adults. Finally, a control group (group 3) consisted of 25 healthy people. PTA and tympanometry were used to evaluate hearing while VNG was used to evaluate vestibular system in all subjects included.

Results
Regarding the SNHL there was a statistically significant difference between post-COVID-19 and controls while no statistically significant difference was reported between post-COVID-19 and post-COVID-23 or between post-COVID-23 and controls. Regarding conductive hearing loss there was statistically significant difference between post-COVID-23 and controls with no statistically significant differences between post-COVID-19 and post-COVID-23 or between post-COVID-23 and controls. Regarding the vestibular examination, Statistical analysis revealed significant difference in caloric test results between post-COVID-19 and controls with no statistically significant difference between the post-COVID-19 and post-COVID-23 or between post-COVID-23 and controls.

Conclusions
SNHL was more than CHL in post-COVID 2019. On the other hand, in post COVID-2023 cases CHL was more than SNHL. Also, the severity of symptom decreased from 2019 to 2023. We recommend that COVID patients should proceed with an audio-vestibular evaluation. So that early affection could be detected and managed properly accordingly.
Using Machine Learning Models to Predict Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Rahadian Rayhan Erlangga , Tan Hong Qi , Ho Bryan Shihan , Kumaran Arjunan , Villanueva Andre , Sng Joy , Tan Ryan Shea Ying Cong , Tan Tira Jing Ying , Tan Veronique Kiak Mien , Tan Benita Kiat Tee , Lim Geok Hoon , Cai Yiyu , Nei Wen Long , Wong Fuh Yong 
Published: November 2024

PURPOSE
Neoadjuvant chemotherapy (NAC) is increasingly used in breast cancer. Predictive modeling is useful in predicting pathologic complete response (pCR) to NAC. We test machine learning (ML) models to predict pCR in breast cancer and explore methods of handling missing data.

METHODS
Four hundred and ninety-nine patients with breast cancer treated with NAC in two centers in Singapore (National Cancer Centre Singapore [NCCS] and KK Hospital) between January 2014 and December 2017 were included. Eleven clinical features were used to train five different ML models. Listwise deletion and imputation were evaluated on handling missing data. Model performance was evaluated by AUC and calibration (Brier score). Feature importance from the best performing model in the external testing data set was calculated using Shapley additive explanations.

RESULTS

Seventy-two (24.6%), 18 (24.7%), and 31 (24.8%) patients attained pCR in NCCS training, NCCS testing, and KK Women's and Children's Hospital (KKH) testing data sets, respectively. The random forest (RF) base and imputed models have the highest AUCs in the KKH cohort of 0.794 (95% CI, 0.709 to 0.873) and 0.795 (95% CI, 0.706 to 0.871), respectively, and were the best calibrated with the lowest Brier score. No statistically significant difference was noted between AUCs of the base and imputed models in all data sets. The imputed model had a larger positive predictive value (PPV; 98.2%
v
95.1%) and negative predictive value (NPV; 96.7%
v
90.0%) than the base model in the KKH data set. Estrogen receptor intensity, human epidermal growth factor 2 intensity, and age at diagnosis were the three most important predictors.

CONCLUSION
ML, particularly RF, demonstrates reasonable accuracy in pCR prediction after NAC. Imputing missing fields in the data can improve the PPV and NPV of the pCR prediction model.
MBX 2109, A Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-In-Human, Randomized Trial
Authors: Carney Patricia , Cutler Gordon B , Schneider Kristi , Zhang Fa , DiMarchi Richard 
Published: November 2024

Abstract

Context
Hypoparathyroidism denotes parathyroid hormone (PTH) deficiency and impaired mineral metabolism. MBX 2109, a novel prodrug yielding a biologically active PTH peptide agonist (PTH[1-32], extended by a fatty acylated Lys33), is being developed as a long-acting, once-weekly PTH replacement therapy.

Objective
Here, we report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MBX 2109 in healthy volunteers.

Methods
This phase 1, randomized, double-blind, placebo-controlled, multiple ascending-dose study (NCT05158335) enrolled healthy adults, who were randomly assigned 4:1 to receive MBX 2109 (200, 400, 600, and 900 μg; n = 8) or placebo (n = 2) by subcutaneous administration once weekly for 4 doses (days 1, 8, 15, and 22). The primary end point was safety and tolerability. Key secondary end points were PK and PD.

Results
Overall, 40 participants (MBX 2109 n = 32, placebo n = 8) were randomly assigned (mean age, 43.3 years; 22.5% female). Treatment-emergent adverse events (TEAEs) occurred in 50% to 88% of MBX 2109 groups and in 25% of placebo participants. In the MBX 2109 groups, no severe or serious TEAEs were observed. Injection-site reaction was the most common treatment-related TEAE. The half-lives were 79 to 95 hours for MBX 2109 and 184 to 213 hours for the fatty-acylated biologically active PTH peptide, which showed dose- and time-dependent exposure increases.

Conclusion
The sustained-action PTH prodrug MBX 2109 was well tolerated with no unexpected, off-target safety issues. The long half-life and flat exposure profile of MBX 2109's biologically active PTH agonist supports once-weekly administration. MBX 2109 doses were identified for future studies.
Social Determinants of Health for Cardiovascular-Kidney-Metabolic Syndrome Among Patients With Diabetes
Authors: Belay Kibret Enyew , Feleke Yeweyenhareg , Alemneh Theodros Aberra , Haile Asteway Mulat , Abebe Dawit Girma 
Published: November 2024

Abstract

Context
Cardiovascular-kidney-metabolic (CKM) syndrome is a recently introduced term that is a complex disease consisting of cardiovascular disease, renal disease, obesity, and diabetes. The association of social determinants of health (SDOH) with CKM syndrome is not fully known.

Objective
We aimed to assess SDOH affecting CKM syndrome among adult patients with diabetes at follow-up at a tertiary hospital in Ethiopia.

Methods
A cross-sectional hospital-based study was used. Data were collected using a Kobo toolbox and entered into SPSS version 29 for further analysis.

Results
A total of 422 adult patients with diabetes were included in this study. The mean ± SD age of the patients was 54.14 ± 13.74 years. Fifty-two percent of the patients were male. In this study, 52.4% had cardiovascular kidney metabolic syndrome. Male patients (AOR: 1.73; 95% CI, 1.01-2.94), lost to follow-up for more than a year due to lack of money (AOR: 2.69; 95% CI, 1.01-7.22), missed an appointment due to lack of transportation in the past 1 year (AOR: 2.98; 95% CI, 1.21-7.33), were patients with disability (AOR: 1.97; 95% CI, 1.12-3.48), had hypertension (AOR: 3.12; 95% CI, 1.85-5.28), had obesity (AOR: 2.27, 95% CI, 1.17, 4.40), and were in retirement (AOR: 2.12; 95% CI, 1.04-4.30) these being more significantly associated with CKM syndrome.

Conclusion
More than half of patients had CKM syndrome. More attention should be given to SDOH, including male sex, financial constraints, transportation issues, disability, and retirement.
Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma
Authors: Blair Alex B. , Radomski Shannon N. , Chou Joanne , Liu Mengyuan , Howell Thomas Clark , Park Wungki , O’Reilly Eileen M. , Zheng Lei , Balachandran Vinod P. , Wei Alice C. , Kingham T. Peter , D’Angelica Michael I. , Drebin Jeffrey , Zani Sabino , Blazer Dan G. , Burkhart Richard A. , Burns William R. , Lafaro Kelly J. , Allen Peter J. , Jarnagin William R. , Lidsky Michael E. , He Jin , Soares Kevin C. 
Published: November 2024

Abstract

Background
Pancreatic acinar cell carcinoma (pACC) is a rare neoplasm of the exocrine pancreas. There is a dearth of information about tumor characteristics and patient outcomes. This study describes the clinical characteristics, genetic alterations, and survival outcomes of resected pACC.

Patients and Methods
Consecutive patients undergoing pancreatectomy for pathologically confirmed pACC from 1999 to 2022 across three high-volume pancreas surgery centers were analyzed. Patient demographics, tumor characteristics, treatment data, and genetic sequencing were obtained through retrospective abstraction.

Results
A total of 61 patients with resected pACC were identified. Median overall survival (OS) was 73 months and median recurrence free survival was 22 months. Nine patients underwent resection for oligometastatic disease; median OS was not reached after a median follow-up of 31 months from date of metastasectomy. Adjuvant chemotherapy was administered in 67% of patients with FOLFOX/FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, ± irinotecan) the most common regimen (58%). Sequencing data were obtained in 47 (77%) patients. A mutation in at least one of three core genes associated with the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, or PALB2) occurred in 26% (n = 12) with BRCA2 the most frequently identified. A mutation in any other “non-core” gene associated with DNA damage repair or the HRR pathway was identified in 45% (n = 21) with a high tumor mutational burden of > 10 mutations per megabase in 13%.

Conclusions
Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
Laparoscopic Subtotal Splenectomy: A Feasible Option in the Treatment of Splenic Metastasis
Authors: Izquierdo Cristina , García-Picazo Alberto , Rodríguez Juan Pablo , Navarro Anna , Donisi Greta , Luque Eduardo , Ielpo Benedetto , Burdío Fernando , Sánchez-Velázquez Patricia 
Published: November 2024

Abstract
Introduction
Laparoscopic subtotal splenectomy (LSS) is a procedure that helps avoid the consequences of asplenia. Given the spleen’s importance and functionality, there may be specific indications and patient conditions in which partial splenectomy is beneficial. This case report aims to clarify the indications for LSS and outline the surgical technique.

Methods
This multimedia article provides a comprehensive overview of the surgical procedure, emphasizing key steps to avoid postoperative bleeding and complications.

Results
The patient was hospitalized for 3 days without any complications observed. Postoperative hemoglobin levels were 11.2 g/dL, with no signs of anemia. The patient was discharged with a follow-up visit after 2 weeks, showing no evidence of postoperative complications. The anatomopathological study revealed a nodular area with extensive tumoral necrosis.

Discussion
LSS is a safe surgical option that might help to mitigate the consequences of total splenectomy. Innovative technology in hemostasis, such as COOLINGBIS© (a monopolar electrosurgical electrode designed for hemostatic sealing and coagulation) can help manage this risk. Identifying the vascular pedicle via computed tomography scan is crucial to prevent unexpected bleeding.

Conclusions
In selected cases, LSS is a feasible and safe procedure when performed with appropriate laparoscopic equipment and by experienced surgeons.
APPROACHES FOR THE TREATMENT OF COMPLICATIONS FOLLOWING WAR INJURIES IN UKRAINIAN PATIENTS
Authors: Pidgaiska Olga , Goumenos Stavros , Dos Santos Maria Virginia , Trampuz Andrej , Stöckle Ulrich , Meller Sebastian 
Published: November 2024

IntroductionSince the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens.Material and MethodsWe conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment.ResultsAll 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection.ConclusionWar injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers.
NANOSCALE ZINC-SUBSTITUTED HYDROXYAPATITE: A BONE GRAFTING BIOMATERIAL WITH ENHANCED ANTIBACTERIAL PROPERTIES
Authors: Wali Rofida , Miller Cheryl , Harrison Caroline , Stafford Graham , Hatton Paul 
Published: November 2024

IntroductionIn specific conditions, infection may lead to bone loss and is difficult to treat1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery.Aim & ObjectivesThe incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity.MethodZinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing(2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant.ResultsXRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation.ConclusionThe results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection.
WHAT DO WE REALLY KNOW ABOUT HAND DISINFECTION PERFORMANCE DURING PATIENT CARE ON SURGICAL WARDS?
Authors: Otchwemah Robin , Sons Dominik , Herbrand Swetlana , Stolte Marieke , Hamid Adnan , Mattner Frauke 
Published: November 2024

AimHand-disinfection (HD) is the most effective infection-prevention-measure. HD-performance of health care professionals (HCP) is usually evaluated by compliance observations (CO). The Hawthorne effect (HE) (HCP behave differently under observation) is considered to systematically increase HD-compliance-rates during CO. However, little is known about the specifications of the HE in health care settings. We hypothesized that, due to hand-hygiene`s known impact on patient safety and infection-prevention, the HE does not affect HD performance during direct patient care in patient-rooms.MethodWe conducted a prospective observational trial on an 18-bed surgical intensive care unit (ICU), a 12-bed surgical intermediate care unit (IMC) and a 36-bed surgical normal ward (NW) in a university hospital in Germany. Dispensers of hand sanitizers were equipped with an electronic monitoring system (EMS) (GWA Hygiene, Germany), which recorded the number of HDs per patient hour (HD/PH) and time and location of hand-disinfections. Locations were categorized as follows: 1. Patient rooms (PR); 2. Utility- and waste-disposal-rooms (UWR) and 3. Other rooms (hallways, kitchen, toilets etc.) (OR). Additionally trained infection-control-staff performed hand-hygiene CO according to WHO's Five Moments. The HD/PH during CO was compared to the HD/PH during the same time-periods without CO. Additionally the ratio between HD/PD-change during CO and mean-HD/PD of each ward during the study-period was determined in percentages. Descriptive and analytical statistics were calculated using R. P-values ≤ 0.05 were regarded as significant.Results587.128 HD were electronically recorded during the study-period (February 2022 to May 2023) and CO took place on 72 days. We recorded a significant increase of HD/PH during CO on all three wards in PRs (ICU: 21%, p<0.001; IMC: 11%, p=0.029; NW: 49%, p=0.047). Furthermore we detected a significant increase of HD/PH during CO on ICU (10%, p<0.001) and IMC (11%, p=0.033) in ORs. CO did not significantly affect HD/PH in ORs on NW and in UWR on all three wards.ConclusionsIn our setting, the number of hand-disinfections per patient-hour was significantly increased during compliance-observations especially in patient-rooms, where hand-hygiene is most crucial for infection-prevention. This indicates a lower everyday compliance to WHO`s hand-hygiene indications during patient care than determined by compliance-observations.AcknowledgmentsPaul-Hartmann AG financially supported this study.
PREVENTING PERIPROSTHETIC JOINT INFECTION: A NOVEL ANTIMICROBIAL SOL-GEL APPROACH
Authors: Boyce Sarah , Nichol Tim , Smith Thomas , Le Maitre Christine 
Published: November 2024

AimPeriprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery.MethodReduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture.ResultsLow antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml-1 tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel.ConclusionsThe ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation.