bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tensor Tympani and Stapedial Tendon Reconstruction for Postoperative Hyperacusis after Tendon Lysis for Middle Ear Myoclonus
Authors: Khandalavala Karl R. , Dornhoffer James R. , Poling Gayla L. , Driscoll Colin L. 
Published: March 2024

Objective
To present a method for repair of the stapedial and tensor tympani tendons in a patient with hyperacusis after a tendon lysis procedure.

Patients
A 71-year-old professional musician who presented to clinic with debilitating hyperacusis following a tensor tympani and stapedial tendon lysis procedure to treat middle ear myoclonus.

Interventions
A novel procedure for reapproximation of the tensor tympani and stapedial tendons into their native insertion points using periosteal grafts and nitinol wire.

Main Outcomes Measures
Stapedial reflex measurements, uncomfortable loudness level, and subjective patient experience.

Results
Postoperatively, the patient had objective improvement in hyperacusis with return of acoustic reflexes in the affected ear and durable improvements in their frequency-specific uncomfortable loudness levels.

Conclusions
This case describes the debilitating complication of hyperacusis following tendon lysis and highlights the importance of maximizing behavioral and medical measures prior to undergoing surgical intervention for middle ear myoclonus.
Morphology of the Dorsal Pancreatic Artery and Its Oncological Significance in Pancreatic Cancer
Authors: Kyuno Takahiro , Makino Isamu , Kitagawa Hirohisa , Terakawa Hirofumi , Gabata Ryosuke , Tokoro Tomokazu , Takada Satoshi , Okazaki Mitsuyoshi , Nakanuma Shinichi , Ohta Tetsuo , Yagi Shintaro 
Published: March 2024

Objectives
Although the dorsal pancreatic artery (DPA) is an important artery that supplies the pancreas, its morphology has not been sufficiently studied. We investigated the morphology of the DPA and the progression of pancreatic cancer along this vessel.

Materials and Methods
Overall, 142 patients with pancreatic cancer who underwent surgical resection at Kanazawa University Hospital between 2004 and 2015 were enrolled. We examined the morphology of the DPA using preoperative computed tomography and cancer progression along the DPA using resected specimens. We investigated the anatomical structures surrounding the DPA through cadaveric examination.

Results
The analysis of computed tomography images revealed the presence of the DPA in 141 patients. In typical cases, the DPA divides into a head and a body branch. Histopathological examination revealed cancer progression along the DPA in 32 patients. Cancer progression along the DPA was identified as a factor associated with a poor prognosis in pancreatic head or body cancer. Cadaveric examination showed the presence of abundant nerve and lymphatic tissues along the DPA.

Conclusions
It is important to remove the soft tissue surrounding the DPA during surgery for pancreatic head or body cancer because it may serve as an important route for cancer progression.
Important Radiologic and Clinical Factors for Predicting Overall Survival in Pancreatic Adenocarcinoma Patients Who Underwent FOLFIRINOX
Authors: Park Sae-Jin , Kim Jung Hoon , Choi Seo-Youn , Joo Ijin 
Published: March 2024

Background
To predict poor overall survival (OS) in pancreatic adenocarcinoma (PAC) who underwent FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) using clinical and computed tomography (CT) findings.

Methods
A total of 189 patients with PAC who received FOLFIRINOX were retrospectively included. Two reviewers assessed CT findings and resectability based on National Comprehensive Cancer Network guidelines. They determined tumor size changes according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Delta measurements were performed. Clinical results, such as whether to perform surgery, were also investigated. A Cox proportional hazard model was used to identify significant predictors for OS. A CT-based nomogram was constructed to predict OS.

Results
Seventy-four patients (39.2%) underwent surgery. For OS, rim enhancement of PAC on baseline CT (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.10–2.77; P = 0.018), high delta tumor on baseline CT (HR, 2.46; 95% CI, 1.55–3.91; P < 0.001), progressive disease at follow-up CT (HR, 8.89; 95% CI, 2.94–26.87; P < 0.001), and without surgery (HR, 2.81; 95% CI, 1.49–5.30; P = 0.001) were important features related to poor prognosis. The nomogram showed good predictive ability for the survival.

Conclusion
Both clinical and CT findings were useful for predicting OS after FOLFIRINOX in PAC.
Second Recurrence of a Mitotically Active Cellular Fibroma From the Ovary
Authors: Wilkerson Casey , Barr Emma , Shahmohamady Babac , Abidi Alireza 
Published: March 2024

BACKGROUND:
Mitotically active cellular fibroma is a benign fibromatous tumor of the ovary. It has 4 or more mitoses/10 high-power fields like a malignant sarcoma but has low-grade nuclear characteristics. Treatment is surgical excision, and recurrence is rare.

CASE:
We present a primary and secondary recurrence of mitotically active cellular fibroma. This patient was a 65-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a large mitotically active cellular fibroma. She then had recurrences of the tumor 5 and 10 years later, requiring repeat resections.

CONCLUSION:
We recommend continued follow-up with these patients given the possibility for delayed recurrence and because follow-up and preventative treatment for these tumors are not well studied.
Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections*
Authors: Karsies Todd , Shein Steven L. , Diaz Franco , Vasquez-Hoyos Pablo , Alexander Robin , Pon Steven , González-Dambrauskas Sebastián ,   with the Bronchiolitis And COdetectioN (BACON) Study Investigators; for the Bronchiolitis Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network and the Red Colaborativa Pediátrica de Latinoamérica Network
Published: March 2024

OBJECTIVES:
To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration.

DESIGN:
Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration.

SETTING:
PICUs in 12 high and low/middle-income countries.

PATIENTS:
Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% (n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684–1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value.

CONCLUSIONS:
Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.
Bacterial cholesterol-dependent cytolysins and their interaction with the human immune response
Authors: Sanford Tristan C. , Tweten Rodney K. , Abrahamsen Hunter L. 
Published: March 2024

Purpose of review
Many cholesterol-dependent cytolysin (CDC)-producing pathogens pose a significant threat to human health. Herein, we review the pore-dependent and -independent properties CDCs possess to assist pathogens in evading the host immune response.

Recent findings
Within the last 5 years, exciting new research suggests CDCs can act to inhibit important immune functions, disrupt critical cell signaling pathways, and have tissue-specific effects. Additionally, recent studies have identified a key region of CDCs that generates robust immunity, providing resources for the development of CDC-based vaccines.

Summary
This review provides new information on how CDCs alter host immune responses to aid bacteria in pathogenesis. These studies can assist in the design of more efficient vaccines and therapeutics against CDCs that will enhance the immune response to CDC-producing pathogens while mitigating the dampening effects CDCs have on the host immune response.
Infectious mononucleosis: new concepts in clinical presentation, epidemiology, and host response
Authors: Naughton Patrick , Enright Frances , Lucey Brigid 
Published: March 2024

Purpose of review
Infectious mononucleosis (IM) is an infectious disease that presents clinically in only a small percentage of individuals despite almost universal infection with the causative agent. Here, we review the latest concepts in the clinical presentation, epidemiology, and host response of this disease.

Recent findings
Several recently published papers/reviews describe IM as a condition caused by one of several etiologic agents including, cytomegalovirus (HHV-5), Roseola virus (HHV-6) and Toxoplasmosis amongst others; this review focuses on IM as solely caused by the human herpes virus 4 (HHV-4). Since the initial discovery of the virus in the 1960s and its subsequent discovery as the primary etiologic agent for IM it has been associated with several human cancers and autoimmune disorders. Recent published findings show a correlation between HHV-4 and the autoimmune disorder, multiple sclerosis (MS), suggesting earlier IM could possibly act as a causative factor. Considering the important links being made with IM to so many cancers and autoimmune disorders it is surprising that a standard investigative procedure has yet to be determined for this disease. A standard approach to the investigation of IM would ensure more cases are diagnosed, particularly atypical cases, this would benefit epidemiological studies, and more immediately help practitioners distinguish viral from bacterial throat infections, enabling them to treat accordingly.

Summary
The understanding of the latest concepts in clinical presentation, epidemiology and host response to IM would benefit greatly from the introduction of a standard procedure for its investigation and diagnosis.
HIV envelope trimers and gp120 as immunogens to induce broadly neutralizing antibodies in cows
Authors: Altman Pilar X. , Parren Mara , Sang Huldah , Ozorowski Gabriel , Lee Wen-Hsin , Smider Vaughn V. , Wilson Ian A. , Ward Andrew B. , Mwangi Waithaka , Burton Dennis R. , Sok Devin 
Published: March 2024

AbstractThe study of immunogens capable of eliciting broadly neutralizing antibodies (bnAbs) is crucial for the development of an HIV vaccine. To date, only cows, making use of their ultralong CDRH3 loops, have reliably elicited bnAbs following immunization with HIV Envelope trimers. Antibody responses to the CD4 binding site have been readily elicited by immunization of cows with a stabilized Env trimer of the BG505 strain and, with more difficulty, to the V2-apex region of Env with a cocktail of trimers. Here, we sought to determine whether the BG505 Env trimer could be engineered to generate new bnAb specificities in cows. Since the cow CD4 binding site bnAbs bind to monomeric BG505 gp120, we also sought to determine whether gp120 immunization alone might be sufficient to induce bnAbs. We found that engineering the CD4 binding site by mutation of a key binding residue of BG505 HIV Env resulted in a reduced bnAb response that took more immunizations to develop. Monoclonal antibodies isolated from one animal were directed to the V2-apex, suggesting a re-focusing of the bnAb response. Immunization with monomeric BG505 g120 generated no serum bnAb responses, indicating that the ultralong CDRH3 bnAbs are only elicited in the context of the trimer in the absence of many other less restrictive epitopes presented on monomeric gp120. The results support the notion of a hierarchy of epitopes on HIV Env and suggest that, even with the presence in the cow repertoire of ultralong CDRH3s, bnAb epitopes are relatively disfavored.
Habitat fragmentation enhances microbial collective defence
Authors: Verdon Nia , Popescu Ofelia , Titmuss Simon , Allen Rosalind J. 
Published: March 2024

AbstractMicrobes often inhabit complex, spatially partitioned geometries such as host tissue or soil, but the effects of habitat fragmentation on microbial infection dynamics and ecology are poorly understood. Here we investigate how habitat fragmentation impacts a prevalent microbial collective defence mechanism: enzymatic degradation of an environmental toxin. Using a theoretical model, we predict that habitat fragmentation can strongly enhance the collective benefits of enzymatic toxin degradation. For the clinically relevant case whereβ-lactamase producing bacteria mount a collective defence by degrading aβ-lactam antibiotic, we find that realistic levels of habitat fragmentation can allow a population to survive antibiotic doses that would far exceed those required to kill a non-fragmented population. This “habitat-fragmentation rescue” is a stochastic effect that originates from variation in bacterial density among different subpopulations and demographic noise. In contrast, the stochastic effects of habitat fragmentation are weaker in a model of collective enzymatic nutrient foraging. Our model suggests that treatment of a spatially complex, fragmented infection showing collective resistance may be far less effective than expected based on bulk population assumptions. This may help to explain lack of correlation between lab-measured antibiotic susceptibility values and clinical treatment success.
Unlocking the Genetic Potential ofSolanum bulbocastanum(SB22, Selection 22): A Valuable Resource for Enhancing Disease Resistance in Commercial Potato Cultivars
Authors: Shanmugavel Senthilkumar , Vinning Kelly , Talbot Sam C. , Brown Charles R. , Sathuvalli Vidyasagar 
Published: March 2024

AbstractCultivated potatoes are susceptible to a host of diseases caused by various pathogens. Wild relatives of potatoes are used in breeding programs as sources of resistance introgressed into cultivated potatoes. The wild potatoSolanum bulbocastanumis an essential source of resistance to Columbia root knot nematode (CRKN) and late blight. We present the initial chromosome-level assembly of SB22, produced using PacBio long reads and Dovetail Hi-C scaffolding. The final assembly size was 655.3 Mb. Using the BRAKER pipeline, 43,280 gene models were predicted, with a BUSCO completeness of about 90.3%. Repeat elements represented 63.8% of the genome, with LTR elements being the most abundant. DRAGO3 predicted 2,310 disease resistance-like genes across the 12 chromosomes of SB22; the MEME suite was used to identify their amino acid motifs. Putative candidate genes contributing to CRKN resistance were mapped on chromosome 11 of SB22. The SB22 draft genome is a valuable genomic resource for potato breeding programs.
FIS103, a Novel SULT1A1-dependent Prodrug, Demonstrates Potent Antitumor Activity in Renal Cell Carcinoma
Authors: Hamilton Ross A. , Saini Uksha , Tran Mai , Foley Christopher J. , Enagala Pooja , Chibas Leniher C. , Chatterjee Disha , Vega Stephanie P. , Chatterjee Dev , Varadhachary Atul 
Published: March 2024

AbstractIntra-tumoral heterogeneity has been shaping the field of precision medicine for cancer patients ever since its emergence. Prodrugs, which require activation by tumor associated enzymes (TAEs), are a rapidly emerging approach for targeted therapeutics. SULT1A1, a sulfotransferase enzyme and TAE, is over-expressed in about 5-15% of cancer patients including breast, prostate and renal cell carcinoma (RCC); however, it is either not expressed or expressed at low level in most normal tissue. Bioinformatic RNA analyses revealed that SULT1A1 over-expression in tumors is correlated with worse patient prognosis. We have identified a new compound, FIS103, which is a small molecule anti-cancer prodrug that is activated by SULT1A1 once internalized. This class of compounds, N-benzyl indole carbinols (N-BICs), cause rapid cell death by inducing widespread non-specific covalent alkylation of proteins in the cancer cell. We report that FIS103 displays potent antitumor activity in SULT1A1 over-expressing RCC cell lines (A498 and Caki-1). Contrarily, low SULT1A1 expressing RCC cells (786-O and ACHN) did not show any antitumor effects, which suggests low FIS103 toxicity in the absence of SULT1A1.In silicomodeling validated the predicted SULT1A1-FIS103 interaction. Furthermore, FIS103 demonstrates potent SULT1A1-dependent antitumor activity in NU/J mouse xenografts injected with A498 cells. Remarkably, the flank tumors in mice regressed to non-measurable 14 days post-FIS103 treatment and did not regrow through the study conclusion. Additionally, SD rats treated with FIS103 once daily for 14 days demonstrated a promising liver toxicity profile with serum liver enzymes falling within the normal range and histopathology analysis indicated no difference between FIS103 or vehicle treated rats. We hereby demonstrate that FIS103 may have the potential to improve survival as well as quality of life of RCC patients and its application could be extended to other SULT1A1 expressing cancers.
Proteomics analysis of peripheral blood monocytes from patients in early dengue infection reveals potential markers of subsequent fluid leakage
Authors: Perera Nilanka , Kumar Abhinav , Gangadharan Bevin , Ranasinghe Diyanath , Wijewickrama Ananda , Malavige Gathsaurie Neelika , Miller Joanna L. , Zitzmann Nicole 
Published: March 2024

AbstractInfections caused by dengue virus (DENV) cause significant morbidity and mortality worldwide. The majority of patients have a mild course of dengue fever (DF) disease, however a proportion of infected individuals develop much more severe dengue haemorrhagic fever (DHF) resulting in circulatory collapse and multiorgan failure due to increased vascular permeability. Early detection of individuals likely to develop severe disease could lead to improved outcomes for patients, and help use healthcare resources more efficiently. At present there are no reliable markers during the earlier stages of infection that indicate which patients will go on to develop DHF. Our study was aimed at identifying proteins that are differentially regulated early during disease in peripheral blood monocytes (PBMC) of patients who subsequently develop DHF. Such proteins may also point at cellular pathways implicated in developing vascular leakage. PBMC were isolated from patients with a confirmed dengue infection, lysed and subjected to tandem mass tag mass spectrometry. One hundred and sixty proteins were differentially expressed in DENV-infected samples compared to healthy controls. These were mainly involved in type I interferon signaling, cytokine response, phagocytosis, haemostasis and cell adhesion. PBMC from DHF patients differentially expressed 90 proteins compared to individuals with DF; these were involved in down-regulation of platelet activation and aggregation, cell adhesion and cytoskeleton arrangement pathways. Proteins involved in oxidative stress and p38 MAPK signaling were upregulated in DHF samples during early infection compared to DF samples. The proteins reported here that are differentially regulated in PBMC early during infection could potentially serve as biomarkers to identify patients at risk of developing DHF at an early disease stage. This study also provides important observations on pathways implicated in severe DENV infection.
The impact of positive surgical margin parameters and pathological stage on biochemical recurrence after radical prostatectomy: a systematic review and meta-analysis
Authors: Guo Hong , Zhang Lei , Shao Yuan , An Kunyang , Hu Caoyang , Liang Xuezhi , Wang Dongwen 
Published: March 2024

AbstractBackgroundTo systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP).MethodsA systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity.ResultsThirty studies that included 46,572 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses.ConclusionsPGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.