bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II trial of enfortumab vedotin for locally advanced and metastatic squamous cell carcinoma of the penis.
Authors: Pagliaro Lance C. , Moore Cassandra N. , Tan Winston , Bobek Olivia , Hillman David W. , Gupta Sounak , Tekin Burak , Herrera Hernandez Loren
Published: June 2024

TPS5108

Background: Penile cancer is a devastating malignancy that affects just over 2000 patients per year in the United States and approximately 40,000 worldwide. Metastatic or unresectable penile cancer is rapidly fatal in most cases and there are few effective systemic therapy options.1 There is an urgent need for alternatives to chemotherapy such as immunotherapy or targeted therapy. Enfortumab vedotin (EV) is an antibody-drug conjugate targeting nectin-4 protein on the tumor cell surface and having efficacy in treatment of metastatic urothelial carcinoma.2 Recent studies have demonstrated frequent and strong expression of nectin-4 in penile squamous cell carcinoma (PSCC).3,4 In this setting, Mayo Clinic is leading a phase II trial of EV for advanced PSCC, currently in progress. Methods: This single arm, open-label, two-stage, phase II trial evaluates best overall response rate (BRR) to EV in patients with PSCC regional lymph node involvement or distant metastatic (M1) disease. Participants may have had any prior systemic therapy or be treatment naïve. Previously untreated patients must be ineligible for or have refused surgery or radiotherapy, have N2-N3 disease and are ineligible for or have refused neoadjuvant chemotherapy, or have clinical evidence of M1 disease. Participants will receive treatment with EV until disease progression, withdrawal, death, or limiting toxicity. Participants will receive EV 1.25 mg/kg intravenous on days 1, 8, and 15 of a 28-day cycle, with tumor assessment performed at 8-week intervals. The primary endpoint is the combined BRR of partial and complete responses (whether confirmed or unconfirmed) according to RECIST 1.1. Secondary endpoints are confirmed response rate, duration of response, progression-free survival, overall survival, adverse events, and BRR in HPV related and unrelated subgroups. Stage 1 will consist of 15 participants, and if there are 2 or more responses will proceed to Stage 2 with an additional 10 participants. The trial opened to enrollment in December 2023, and is active at Mayo Clinic sites in Minnesota, Arizona, and Florida. Clinical trial information: Funding and drug supplied by Astellas Pharma Global Development, Inc./Seagen Inc. NCT06104618. 1. Chahoud J, et al., Curr Opin Urol. 2022 Jan 1;32(1):8-16. 2. Powles T, et al. N Engl J Med. 2021 Mar 25;384(12):1125-1135. 3. Tekin B, et al. Hum Pathol. 2023 Dec;142:42-50. 4. Grass GD, et al. Eur Urol Open Sci. 2023 Jan 10;49:1-5. Clinical trial information: NCT06104618 .
ProstACT GLOBAL: A phase 3 study of best standard of care with and without 177Lu-DOTA-rosopatamab (TLX591) for patients with PSMA expressing metastatic castration-resistant prostate cancer progressing despite prior treatment with a novel androgen axis drug.
Authors: Sartor Oliver , Tagawa Scott T. , Lenzo Nat , Cade David , Agarwal Neeraj
Published: June 2024

TPS5115

Background: The treatment of advanced prostate cancer (PC) is challenging, with no curative therapy to date and undesirable side effects that may impact patient quality of life. Monoclonal antibodies enable high specificity with low rates of off-target organ exposure, prolonged retention in PSMA+ tumors, and a predictable safety profile. There is a strong rationale for further investigation of the 177Lu-labeled, chelator-conjugated antibody, 177Lu-DOTA-rosopatamab (hereafter, TLX591), with prior studies demonstrating a favorable safety profile and efficacy, particularly with a fractionated (dose-dense) regimen Phase 1 ProstACT SELECT preliminary results demonstrate consistent uptake between TLX591 and 68Ga-PSMA-11 imaging and reinforces advantages of this first-in-class radio-antibody drug conjugate investigational therapy. Methods: In this multinational, multicenter, prospective, randomized, open label phase 3 study, patients (N=400) with PSMA-expressing metastatic castration-resistant PC (mCRPC) that have progressed despite prior treatment with an androgen-receptor pathway inhibitor (ARPI) will be enrolled in a 2:1 ratio to receive best protocol-defined standard of care (SoC) with or without 2 intravenous injections of 2.8 GBq of TLX591, given 14 days apart. SoC may be alternative ARPI or docetaxel. Eligible patients must have received 1 prior ARPI in the mCSPC, nmCRPC, or 1L mCRPC setting. Patients must have 150x109 /L platelets, and have PSMA-positive disease on 68Ga-PSMA-11 PET/CT imaging. The primary endpoint is radiographic progression-free survival. Secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, health-related quality of life, and treatment-related adverse events count. An alpha control and 95% confidence intervals will be used; patients will be substratified between TLX591 + 2nd ARPI or TLX591 + docetaxel. This study is currently enrolling. This study is funded by Telix Pharmaceuticals. Clinical trial information: NCT04876651 .
Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with new hormonal agents in patients with metastatic castration-sensitive prostate cancer with and without homologous recombination repair mutation (EvoPAR-Prostate01).
Authors: Chi Kim N. , Agarwal Neeraj , Armstrong Andrew J. , Hellmis Eva , Schlürmann Friederike , Sugimoto Mikio , Ürün Yüksel , Xing Nianzeng , Aregay Mehreteab , Lima Julianne , Meulendijks Didier , Azad Arun
Published: June 2024

TPS5123

Background: PARP inhibitors (PARPi) in combination with new hormonal agents (NHAs) are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). PARPi utilization in earlier lines of treatment may result in greater magnitude of benefit. Saruparib is a potential best-in-class PARPi, which selectively inhibits and traps PARP1, has minimal effect on PARP2, and hence may offer an improved therapeutic window compared with currently approved nonselective PARPi. The efficacy and safety of saruparib plus NHAs for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) and mCRPC are being assessed in the phase I/IIa PETRANHA study (NCT05367440). The phase III EvoPAR-Prostate01 study (NCT06120491) is evaluating the efficacy and safety of saruparib plus physician’s choice of NHA (abiraterone, darolutamide, or enzalutamide) compared with placebo plus physician’s choice of NHA in participants with mCSPC. Methods: This is a 2-cohort, 2-arm, randomized, double-blind, placebo-controlled, multicenter global study. Key eligibility criteria include age ≥18 years, histologically confirmed mCSPC ( de novo or recurrent low- or high-volume disease), ECOG PS 0-1, and confirmed, prospectively defined homologous recombination repair gene mutation (HRRm) status (defined by the presence/absence of pathogenic/likely pathogenic mutations in ≥1 of the genes BRCA1, BRCA2, ATM, CDK12, PALB2, RAD51B, RAD51C, RAD51D,and BARD1). Participants must be receiving androgen deprivation therapy throughout the study or have undergone bilateral orchiectomy, and must be suitable for treatment with NHAs. Key exclusion criteria include prior therapy with PARPi, prior chemotherapy or NHAs in the mCSPC setting (prior NHAs for localized disease permitted), and history of, or suspected, myelodysplastic syndrome/acute myeloid leukemia. Participants are allocated to either the HRRm or non-HRRm cohort based on prospective testing of both tumor tissue and circulating tumor DNA. Participants are randomized 1:1 to receive saruparib plus physician’s choice of NHA or placebo plus physician’s choice of NHA. Treatment continues until disease progression, unacceptable toxicity, or participant-initiated withdrawal. The primary endpoint is radiographic progression-free survival (rPFS), with overall survival (OS) a key secondary endpoint. Planned statistical analyses of rPFS and OS will be conducted within each cohort using a stratified log-rank test. Approximately 1,800 participants (550 HRRm; 1,250 non-HRRm) will be randomized. Enrollment began in November 2023 and is ongoing. Clinical trial information: NCT06120491 .
Randomized PROSTATE-IQ trial to reduce ADT treatment burden for patients with biochemical recurrence after prostatectomy.
Authors: Hoffman Karen E. , Kollmeier Marisa , Nguyen Paul L.
Published: June 2024

TPS5130

Background: Men with PSA recurrence of prostate cancer after prostatectomy often receive Androgen Deprviation Therapy (ADT) with salvage radiation therapy to the prostate resection bed. Traditional ADT improves cancer control; however, it also causes fatigue, sexual dysfunction, hot flashes, cognitive changes, metabolic dysregulation, body composition changes, and negatively impacts men’s quality of life. Methods: The PROSTATE-IQ trial is a randomized multi-center clinical trial that is investigating ways to reduce the adverse effects of ADT treatment. First, the trial uses intrinsic cancer properties assessed by ArteraAI and clinical-pathologic variables to personalize the intensity of Androgen Axis Therapy (AAT). Those with low ArteraAI score are assigned to the Artera Low Cohort and those with either high ArteraAI score, PSA >0.5 ng/ml or nodal involvement are assigned to the Higher-risk Cohort. Second, the trial randomizes men between traditional ADT and apalutamide-based therapy. We hypothesize that the apalutamide-based therapy will reduce the adverse effects of treatment and thereby improve quality of life. 220 men in the Artera Low Cohort are being randomized between 6 months of ADT vs. 6 months of apalutamide monotherapy. 220 men in the Higher-risk Cohort are being randomized between 24 months of ADT (winning arm of RADICALS-HD trial) vs. 6 months of apalutamide and ADT (winning arm of FORMULA 509 trial). We hypothesize that the apalutamide-based treatments will reduce fatigue and boost activity, sleep, and cognitive function. Patients wear an activity and sleep tracker, undergo cognitive assessments, and complete validated fatigue, leisure activity, and mental health questionnaires. We will compare fatigue, activity, sleep, mental health, body composition, metabolic dysregulation, quality of life, and cancer control between treatment arms. This trial will be impactful because it is the first to use the validated ArteraAI test to personalize intensity of androgen axis therapy and because it will reduce the adverse effects of treatment and improve quality of life for prostate cancer survivors treated with salvage radiation and androgen axis therapy.
Automated Lugano Metabolic Response Assessment in
18
F-Fluorodeoxyglucose–Avid Non-Hodgkin Lymphoma With Deep Learning on
18
F-Fluorodeoxyglucose–Positron Emission Tomography
Authors: Jemaa Skander , Ounadjela Souhila , Wang Xiaoyong , El-Galaly Tarec C. , Kostakoglu Lale , Knapp Andrea , Ku Grace , Musick Lisa , Sahin Denis , Wei Michael C. , Yin Shen , Bengtsson Thomas , De Crespigny Alex , Carano Richard A.D.
Published: June 2024

PURPOSE

Artificial intelligence can reduce the time used by physicians on radiological assessments. For
18
F-fluorodeoxyglucose–avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic.

METHODS

Here, we present a deep learning–based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier:
NCT01287741
) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers
NCT02257567
,
NCT02500407
; 20% holdout in ClinicalTrials.gov identifier
NCT01287741
), outputs the detected lesions at baseline and follow-up to enable focused radiologist review.

RESULTS

The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers
NCT01287741
,
NCT02500407
, and
NCT02257567
, respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers
NCT01287741
,
NCT02500407
, and
NCT02257567
, compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses.

CONCLUSION

These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.
Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis
Authors: Dabhi Nisha , Sokolowski Jennifer , Zanaty Mario , Kellogg Ryan T. , Park Min S. , Mastorakos Panagiotis
Published: June 2024

BACKGROUND AND OBJECTIVES:

The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear.

METHODS:

We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis.

RESULTS:

We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%).

CONCLUSION:

Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.
Cavernous Malformation From Cranial Nerves: A Systematic Review With a Novel Classification and Patient-Level Analysis
Authors: Li Ziyang , Chen Liangpeng , Wang Junmei , Dong Gehong , Jia Guijun , Jia Wang , Li Deling
Published: June 2024

BACKGROUND AND OBJECTIVES:

Cavernous malformations (CMs) occurring in the cranial nerve (CN) are extremely rare, and there is currently no comprehensive review on CN CMs, leading to a lack of sufficient understanding of CN CMs. We aimed to systematically review all published CN CM cases; summarize the epidemiology, clinical manifestations, treatment, and prognosis of CN CMs; and identify factors influencing the prognosis of CN CMs.

METHODS:

This systematic review identified all cases potentially diagnosed with CN CM through a systematic search of PubMed, SCOPUS, Web of Science, and Cochrane databases. This represents the most comprehensive systematic review to date. We classified CN CMs based on their anatomic origins. Patient characteristics, disease manifestations, treatment approaches, and prognosis were summarized descriptively. Further analysis was conducted to identify factors influencing the prognosis of CN CMs.

RESULTS:

The final analysis included 108 articles (127 individual patient cases). The optic nerve (49/128, 38.3%) is the most commonly affected nerve. Notably, CN CMs can be categorized into 3 types: Intraneural, Perineural, and Extraneural. Preoperative nerve function status and novel classification were associated with the prognosis of CN CMs (P = .001; P < .001). The postoperative neurological deterioration rate for the Intraneural type was 19/37 (51.4%); for the Extraneural type, it was 13/69 (18.8%); and for the Perineural type, it was 1/22 (4.5%) (P < .001).

CONCLUSION:

We reviewed all the published CN CMs to date, offering a comprehensive description of CN CMs for the first time and identifying prognostic factors. The classification of CN CMs proposed in this study could serve as guidance for the selection of intraoperative treatment regimens. The findings of this systematic review are expected to provide a foundation for clinical decision-making in this crucial rare disease and lay the groundwork for developing relevant clinical guidelines.
Artificial Intelligence for Automatic Analysis of Shunt Treatment in Presurgery and Postsurgery Computed Tomography Brain Scans of Patients With Idiopathic Normal Pressure Hydrocephalus
Authors: Shailja S. , Nguyen Christopher , Thanigaivelan Krithika , Gudavalli Chandrakanth , Bhagavatula Vikram , Chen Jefferson W. , Manjunath B.S.
Published: June 2024

BACKGROUND AND OBJECTIVES:

Ventriculo-peritoneal shunt procedures can improve idiopathic normal pressure hydrocephalus (iNPH) symptoms. However, there are no automated methods that quantify the presurgery and postsurgery changes in the ventricular volume for computed tomography scans. Hence, the main goal of this research was to quantify longitudinal changes in the ventricular volume and its correlation with clinical improvement in iNPH symptoms. Furthermore, our objective was to develop an end-to-end graphical interface where surgeons can directly drag-drop a brain scan for quantified analysis.

METHODS:

A total of 15 patients with 47 longitudinal computed tomography scans were taken before and after shunt surgery. Postoperative scans were collected between 1 and 45 months. We use a UNet-based model to develop a fully automated metric. Center slices of the scan that are most representative (80%) of the ventricular volume of the brain are used. Clinical symptoms of gait, balance, cognition, and bladder continence are studied with respect to the proposed metric.

RESULTS:

Fifteen patients with iNPH demonstrate a decrease in ventricular volume (as shown by our metric) postsurgery and a concurrent clinical improvement in their iNPH symptomatology. The decrease in postoperative central ventricular volume varied between 6 cc and 33 cc (mean: 20, SD: 9) among patients who experienced improvements in gait, bladder continence, and cognition. Two patients who showed improvement in only one or two of these symptoms had <4 cc of cerebrospinal fluid drained. Our artificial intelligence–based metric and the graphical user interface facilitate this quantified analysis.

CONCLUSION:

Proposed metric quantifies changes in ventricular volume before and after shunt surgery for patients with iNPH, serving as an automated and effective radiographic marker for a functioning shunt in a patient with iNPH.
The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs
Authors: Gayen Anakshi , Mukherjee Avik , Kumar Krishna , Majumder Shubhra , Chakrabarti Saikat , Mukherjee Chandrama
Published: June 2024

The model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5′-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs.
Cryptococcus laurentii fungemia in a patient with chronic kidney disease on hemodialysis
Authors: Siqueira Athayde Lima Rafael , Rodrigues Marçal João Victor
Published: June 2024

Introduction: Chronic Kidney Disease (CKD) is a relevant comorbidity from clinical and public health perspectives. Infections are an important cause of death in those patients. Although rare, fungal infections are increasing in incidence. Case report: a 45-year-old female patient with CKD due to systemic lupus erythematosus (SLE) was admitted to a tertiary hospital due to a bloodstream infection (BSI) caused by Cryptococcus laurentii. She received treatment with anidulafungin with good initial response but presented clinical and laboratory worsening after a few days, and the treatment was switched to amphotericin B. The hemodialysis access was changed. Chest tomography, echocardiogram, eye fundus examination, and cerebrospinal fluid study did not show changes. After 32 days of amphotericin B, the patient presented clinical improvement and was discharged to take oral fluconazole for three (3) months. Conclusion: BSI due to Cryptococcus laurentii is rare in patients on chronic hemodialysis with a high potential for complications. Physicians should have clinical suspicion for those infrequent infections infractions, and culture evaluation should always be performed. The diagnosis is still a challenge, as well as the therapeutic regimen.
Subungual melanoma - what you need to know about it. A literature review
Authors: Niemczyk Anna , Miłek Magdalena , Ślusarczyk Monika , Stawska Weronika , Foryś Angelika , Kwaśniak Ksenia , Magierska Agata , Banach Mariola , Bolla Patrycja , Staś Magdalena
Published: June 2024

Introduction and objective:Melanoma is one of the most malignant skin cancers originating from pigment cells, accounting for 5–7% of all skin cancers. The prognosis, especially in case of late diagnosis, is poor. The aim of the study is to systematise information on subungual melanoma. To raise awareness among the public and professionals working in the skin care sector of the diagnosis, early detection and treatment of subungual melanoma.
Brief description of the state of knowledge: Subungual melanoma originates from subungual melanoma lentigines and constitutes from 0.7% to 3.5% of all malignant melanomas. Among dark-skinned populations, this subtype accounts for up to 30% and is the most common subtype of malignant melanoma among African Americans, Asians, and Latinos. Subungual melanoma occurs asymmetrically, most often affecting the big toe or thumb. In this disease, the starting point are melanocytes, which undergo malignant transformation within the nail matrix. A symptom of the disease may be melanonychia, a streak of pigment or irregular discoloration, eventually it takes the form of a triangle. This symptom indicates an advanced stage of the disease. The basis for making the diagnosis is dermoscopy and biopsy. Grazzini et al. suggest conducting a biopsy in each case where one nail plate is affected and the lesion persists for more than 6 months. An important element of diagnostics that helps diagnose of subungual melanoma is the ABCDEF algorithm. Knowledge of the above-mentioned helps to detect disturbing symptoms at an early stage of the disease, which improves the prognosis and increases the chances of cure.
Summary:Early detection of melanoma gives a better chance of cure, reduces mortality and complications of the disease, therefore any action to increase public knowledge and awareness on the subject is important.
The role of nintedanib and pirfenidone in the treatment of idiopathic pulmonary fibrosis and review of recent clinical trials of IPF therapy
Authors: Żuber Michał , Dąbrowska Paulina , Dacka Michał
Published: June 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic, rare disease characterized by continuous fibrosis of the lung parenchyma. It mainly affects the elderly; however, it is increasingly being diagnosed in younger patients as well. Risk factors include smoking, occupational dust exposure and genetic factors. Symptoms of IPF include shortness of breath, dry cough and reduced exercise tolerance, leading to a reduced quality of life for patients. Diagnosis is based on imaging, mainly high-resolution CT scans, and the exclusion of other causes of interstitial lung disease. Two antifibrotic drugs, nintedanib and pirfenidone, are now approved to slow disease progression. Nintedanib acts as a tyrosine kinase inhibitor, blocking the signaling pathways of lung fibroblasts. Pirfenidone, on the other hand, has anti-inflammatory and anti-fibrotic effects by inhibiting TGF-b signaling pathways. Clinical trials have confirmed their efficacy in reducing the decline in increased vital capacity and the risk of disease progression. In Poland, patients with IPF can benefit from nintedanib and pirfenidone therapy under the drug program. Despite advances in treatment, more research is needed on new IPF therapies. Clinical trials of zinpentraxin, ziritaxestat and pambrevalumab have not confirmed their efficacy in treating IPF. Results from initial studies of bexotegrast show promise, but further studies are needed and are ongoing. Despite advances in the treatment of IPF, further research into new therapies is needed to improve therapeutic outcomes and patient quality of life.
Review of the Literature on Patellar Tendinopathy: Current State of Knowledge
Authors: Milczarek Jakub , Szymczuk Błażej , Iwan Magdalena , Trojanowski Dominik , Adamiec Ksawery , Smorońska-Rypel Joanna , Rodak Małgorzata , Piątkowska Natalia , Kajzar Magdalena , Nitka Kamila
Published: June 2024

Introduction:
Patellar tendinopathy, commonly referred to as jumper’s knee, presents as pain and dysfunction in the patellar tendon, predominantly affecting athletes engaged in jumping sports. The symptoms of patellar tendinopathy not only impact sports involvement but also interfere with activities of daily living, such as climbing stairs and sitting for extended periods, which in turn affects overall well-being. A variety of treatment options are available, encompassing both conservative approaches, such as modifying activity levels and undergoing physical therapy, and surgical methods.
Aim of the study:
The objective of this study is to review the current literature regarding the incidence, risk factors and currently available treatment methods for patellar tendinopathy. In addition, the aim is to present a summary of the knowledge and information collected so far in this area in a concise and accessible format.
State of knowledge:
The epidemiology and mechanisms of patellar tendinopathy are already well documented and described. The statistics regarding the incidence of patellar tendinopathy among athletes in the given fields are sufficiently consistent with each other. The existing literature provides insights into the efficacy of various therapeutic approaches for patellar tendinopathy, yet it is limited in scope.
Conclusion:
This review acknowledges that recent advancements in research have led to a fuller understanding of epidemiology and improvement of treatment methods for patellar tendinopathy. Despite this, a single therapy is not sufficient for optimal outcomes. Therefore, it is recommended that a comprehensive approach to conservative treatment be adopted. Further research and clinical trials are essential for the generation of reliable conclusions.
Personality Disorders – a basic information review
Authors: Waloch Kamil , Łepik Michał , Uszok Zofia , Rosiak Krzysztof , Płeska Kacper , Reguła Kacper , Wojtania Joanna , Piaszczyński Szymon , Czajka Andrzej , Szymański Bartłomiej
Published: June 2024

Personality disorders refer to a collection of mental health conditions defined by persistent deviations from societal norms in thoughts, behaviors, and emotions. These deviations frequently result in challenges in interpersonal relationships, self-perception, and overall functioning, potentially causing distress in various aspects of life. The DSM-5 classifies personality disorders into three clusters. Cluster A contains paranoid, schizoid and schizotypal personality disorders which are characterized by strange and eccentric behaviors. Cluster B contains narcissistic, histrionic and antisocial personality disorders which are characterized by dramatic and emotional behaviors. Cluster C contains avoidant, dependent and obsessive-compulsive personality disorders which are characterized by anxious and fearful behaviors.
Necrotizing Enterocolitis in Newborns: Diagnosis, Etiology, Management, Prevention, Complications and their Relation to Future Sport Performance
Authors: Uszok Zofia , Łepik Michał , Rosiak Krzysztof , Płeska Kacper , Reguła Kacper , Waloch Kamil , Wojtania Joanna , Piaszczyński Szymon , Szymański Bartłomiej , Czajka Andrzej
Published: June 2024

Necrotizing enterocolitis (NEC) is a serious gastrointestinal condition that primarily affects premature infants, although it can also occur in full-term infants. It is characterized by inflammation and injury of the intestinal tissue, which can progress to necrosis and perforation of the bowel. NEC is a leading cause of morbidity and mortality in neonatal intensive care units (NICUs), particularly among very low birth weight infants.
Diagnosis of NEC is based on clinical signs and symptoms, radiographic findings, and laboratory tests. Management of NEC involves a multidisciplinary approach, including supportive care, medical therapy, and surgical intervention when necessary. Supportive care includes bowel rest, intravenous fluids, and nutritional support. Medical therapy may include antibiotics, gastric decompression, and parenteral nutrition. Surgical intervention may be required for infants with intestinal perforation, severe NEC, or complications such as intestinal stricture or short bowel syndrome. This condition and its complications may carry consequences for life and especially sport performance in the child’s future.
Strategies for preventing NEC include promoting breastfeeding, avoiding unnecessary antibiotic exposure, minimizing enteral feeding interruptions, practicing strict infection control measures, and implementing protocols for gradual feeding advancement in premature infants.
Overall, NEC is a complex and multifactorial disease that poses significant challenges in neonatal care. Early recognition, prompt intervention, and comprehensive management are essential for optimizing outcomes for affected infants. Further research is needed to better understand the pathophysiology of NEC and to develop more effective prevention and treatment strategies.
Transfer Reinforcement Learning for Mixed Observability Markov Decision Processes with Time-Varying Interval-Valued Parameters and Its Application in Pandemic Control
Authors: Du Mu , Yu Hongtao , Kong Nan
Published: June 2024

We investigate a novel type of online sequential decision problem under uncertainty, namely mixed observability Markov decision process with time-varying interval-valued parameters (MOMDP-TVIVP). Such data-driven optimization problems with online learning widely have real-world applications (e.g., coordinating surveillance and intervention activities under limited resources for pandemic control). Solving MOMDP-TVIVP is a great challenge as online system identification and reoptimization based on newly observational data are required considering the unobserved states and time-varying parameters. Moreover, for many practical problems, the action and state spaces are intractably large for online optimization. To address this challenge, we propose a novel transfer reinforcement learning (TRL)-based algorithmic approach that ingrates transfer learning (TL) into deep reinforcement learning (DRL) in an offline-online scheme. To accelerate the online reoptimization, we pretrain a collection of promising networks and fine-tune them with newly acquired observational data of the system. The hallmark of our approach comes from combining the strong approximation ability of neural networks with the high flexibility of TL through efficiently adapting the previously learned policy to changes in system dynamics. Computational study under different uncertainty configurations and problem scales shows that our approach outperforms existing methods in solution optimality, robustness, efficiency, and scalability. We also demonstrate the value of fine-tuning by comparing TRL with DRL, in which at least 21% solution improvement can be yielded by TRL with fine-tuning for no more than 0.62% of time spent on pretraining in each period for problem instances with a continuous state-action space of modest dimensionality. A retrospective study on a pandemic control use case in Shanghai, China shows improved decision making via TRL in several public health metrics. Our approach is the first-ever endeavor of employing intensive neural network training in solving Markov decision processes requiring online system identification and reoptimization.

History: Accepted by Paul Brooks, Area Editor for Applications in Biology, Medicine, & Healthcare.

Funding: This work was supported in part by the National Natural Science Foundation of China [Grants 72371051 and 72201047] to the first and second authors and in part by the National Science Foundation [Grant 1825725] to the third author.

Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0236 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0236 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Stable Matching on the Job? Theory and Evidence on Internal Talent Markets
Authors: Cowgill Bo , Davis Jonathan M. V. , Montagnes B. Pablo , Perkowski Patryk
Published: June 2024

A principal often needs to match agents to perform coordinated tasks, but agents can quit or slack off if they dislike their match. We study two prevalent approaches for matching within organizations: centralized assignment by firm leaders and self-organization through market-like mechanisms. We provide a formal model of the strengths and weaknesses of both methods under different settings, incentives, and production technologies. The model highlights trade-offs between match-specific productivity and job satisfaction. We then measure these trade-offs with data from a large organization’s internal talent market. Firm-dictated matches are 33% more valuable than randomly assigned matches within job categories (using the firm’s preferred metric of quality). By contrast, preference-based matches (using deferred acceptance) are only 5% better than random but are ranked (on average) about 38 percentiles higher by the workforce. The self-organized match is positively assortative and helps workers grow new skills; the firm’s preferred match is negatively assortative and harvests existing expertise.

This paper was accepted by Joshua Gans, business strategy.

Funding: This work was supported by the Ewing Marion Kauffman Foundation (Emerging Scholar Award).

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.01373 .
Dynamic Relocations in Car-Sharing Networks
Authors: Hosseini Mahsa , Milner Joseph , Romero Gonzalo
Published: June 2024

In the paper “Dynamic Relocations in Car-Sharing Networks,” researchers have developed a new dynamic car relocation policy aimed at improving the efficiency of car-sharing networks. The policy addresses the challenge of unpredictable and uneven demand across the network by projecting the classical fluid model onto the simpler dimension of relocation decisions. This projection leads to a clearer understanding of the fluid model as a set of linear programs. The effectiveness of this new dynamic policy has been rigorously tested against traditional static policies through extensive simulations. The results are promising, showing that the dynamic policy significantly outperforms its static counterpart, reducing the optimality gap by more than 23% on average. This breakthrough offers substantial potential benefits for car-sharing operations, enhancing their ability to respond adaptively to changing demand and thus optimizing resource allocation and user satisfaction.
Rebouças: o engenheiro negro do Império
Authors: Fernandes Morais Rodrigo , Fontes dos Santos Antonio Carlos
Published: June 2024

Apresentamos neste ensaio uma figura atravessada por questões de identidade racial, que foram determinantes em sua formação como sujeito e consequentemente como homem da ciência1  em sua época: André Pinto Rebouças, o engenheiro negro do Império. Contaremos a sua hist6ria de vida e analisaremos as questões raciais enfrentadas por Rebouças. Apresentaremos também o pouco conhecido ponto de vista do Educador Rebouças sobre a formação completa do engenheiro, assim como, sua visão sobre a finalidade da ciência. Esperamos que educadores e educadoras de física - assim como áreas ligadas às exatas - se inspirem e utilizem este texto histórico para descolonizar/ decolonizar suas práxis educacionais.
MEMÓRIAS DO MOVIMENTO DE MULHERES NEGRAS EM TERESINA, PIAUÍ, BRASIL DOS SÉCULOS XX E XXI
Authors: Alves de Sousa Juliana , SOARES DA SILVA IRANEIDE
Published: June 2024

Este artigo tem por objetivo analisar as trajetórias e experiências políticas, sociais e culturais de mulheres negras, no período compreendido entre os anos de 1980 a 2000, na cidade de Teresina-PI. Supomos que suas trajetórias estão marcadas por uma dinâmica que remete à sua condição diaspórica expressa nos diferentes sentimentos de resistência, luta e pertencimento alicerçados na ancestralidade e na sabedoria africana que são reinterpretados e reinventados cotidianamente no ambiente de diáspora. Ademais, são mulheres que possuem uma práxis que visa não só transformar a vida de outras mulheres negras, mas a própria sociedade, uma vez que quando elas se movimentam toda a estruturas da sociedade se movimentam com elas (DAVIS, 2017).
Pressure ulcers related to prone positioning: a pandemic amidst a pandemic
Authors: Ramirez-Marin Hassiel Aurelio , Contreras-Yañez Irazu , Campos-Jimenez Karin Ivette , Molina-Murrieta Leticia , Huerta-Ramirez Yeni , Domínguez-Cherit Judith Guadalupe
Published: June 2024

Objective:

To explore the epidemiology and risk factors associated with the development of pressure ulcers (PUs) in patients receiving prone positioning (PP) ventilatory therapy; to compare the inflammatory status of patients who develop PUs with those who do not; and to describe the experience and useful findings that have allowed us to improve the management of these patients to reduce the incidence of PUs.

Method:

An observational, descriptive and longitudinal study was conducted, where sociodemographic and laboratory data were collected from patients who were hospitalised and required PP ventilatory therapy in critical care areas (CCA) during the months of May–October 2020.

Results:

From the total number of patients who required PP during their CCA stay (n=240), 202 (84.2%) developed a PU. The four most frequent areas where a PU appeared were: the head and neck (n=115); the pinna (n=21); the torso (n=21); and the lower limbs (n=21). Patients who developed PU were more frequently males with higher initial levels of creatinine phosphokinase and ferritin. The incidence for each month of follow-up decreased from 8.3% to 5.8%.

Conclusion:

Regardless of the intervention, a multidisciplinary approach is required to optimise the prevention and treatment of these wounds. While PUs are often the result of other medical conditions or poor health status in general, the vast majority of PUs are avoidable.
Clinical performance and safety of a debridement pad with abrasive and non-abrasive fibres
Authors: Stürmer Ewa , Debus Eike Sebastian , Atkin Leanne
Published: June 2024

Background:

Debridement is key to removing devitalised tissue, debris and biofilm as part of wound-bed preparation. Unlike many other methods of debridement, mechanical debridement with a pad is effective enough to be used independently without an adjunctive method of debridement, while being more accessible than other standalone options.

Objective:

To explore the clinical performance and safety of a debridement pad with both abrasive and non-abrasive surfaces in daily clinical practice.

Methods:

This was a prospective, non-controlled, non-randomised, single-arm, open-label, multicentred observational evaluation. Inclusion criteria were wounds >4 cm2 covered with at least 30% debris, necrotic tissue or slough in patients aged ≥18 years. The treatment protocol comprised a single application of the debridement pad. The primary outcome measure was the amount of necrotic tissue, slough or debris in the wound bed. Secondary outcomes included the appearance of the wound bed, edges and periwound skin; self-reported pain scores; foreseeable negative impacts; and clinician satisfaction.

Results:

A total of 62 participants with a variety of wound types were included in the analysis. Most wounds (87%) had been present for over 3 months and had high or moderate exudate levels (90%). A significant reduction was observed in all three parameters: necrotic tissue (p=0.043), slough (p<0.001) and debris (p<0.001). Necrotic tissue, slough and debris showed mean relative reductions of 40%, 72% and 40%, respectively. Of participants, 84% did not experience an increase in pain during the debridement procedure.

Conclusion:

This clinical real-world data shows the debridement pad to be an effective and well-tolerated device for debridement and wound bed preparation.
MicroRNA expression analysis in peripheral blood and soft-tissue of patients with periprosthetic hip infection
Authors: Paksoy Alp , Meller Sebastian , Schwotzer Florian , Moroder Philipp , Trampuz Andrej , Imiolczyk Jan-Philipp , Perka Carsten , Hackl Matthias , Plachel Fabian , Akgün Doruk
Published: June 2024

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Methods

This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline.

Results

Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups.

Conclusion

With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI.

Cite this article: Bone Jt Open 2024;5(6):479–488.