variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.

Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study.

Background: Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1.

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study.

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1.

Genetic and Clinical Analyses of the -c.226C>T Variant Resulting in a Dual Mutational Mechanism.

Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of cases.

Delivery mode after cervical ripening among patients with no prior vaginal births.

Purpose: To compare mode of delivery and maternal and neonatal outcomes using cervical ripening balloon (CRB) for induction of labor (IOL) in nulliparous patients vs. those undergoing first trial of labor after cesarean (TOLAC).

Methods: Retrospective cohort study including data from two tertiary medical centers.

Magnetic resonance imaging for acute appendicitis in pregnancy: can clinical scores predict when imaging is needed?

Purpose: Advanced imaging may augment the diagnostic milieux for presumed acute appendicitis (AA) during pregnancy, however it is not clear when such imaging modalities are indicated. The aim of this study was to assess the sensitivity and specificity of clinical scoring systems with the findings on magnetic resonance imaging (MRI) of AA in pregnant patients.

Methods: A retrospective cohort study between 2019 and 2021 was performed in two tertiary level centers.

Cloning, purification and characterization of human dentine matrix protein 1(DMP1).

Introduction: Human teeth are composed mainly of dentin, formed by the odontoblasts. Dentin matrix protein 1 (DMP1) is one of odontoblast differentiation's most important growth factors. Human DMP1 has yet to be completely identified or studied.

The Impact of PSMA PET/CT on Modern Prostate Cancer Management and Decision Making-The Urological Perspective.

Prostate-specific membrane antigen (PSMA) PET use in prostate cancer treatment has recently become a routinely used imaging modality by urologists. New, established data regarding its performance in different stages of prostate cancer, as well as gaining clinical knowledge with new tracers, drives the need for urologists and other clinicians to improve the utilization of this tool. While the use of PSMA PET/CT is more common in metastatic disease, in which it outperforms classical imaging modalities and drives treatment decisions and adjustments, recently, it gained ground in localized prostate cancer as well, especially in high-risk disease.

Dental and maxillofacial injuries associated with domestic violence against women in Israel: A report for 2011-2021.

Background/aim: The WHO, in its 2002 report, indicated the dramatic worldwide increase in the incidence of intentional injuries affecting people of all ages and both sexes, but especially children, women, and the elderly. The aim of this study was to analyze dental and maxillofacial injuries associated with domestic violence against women in Israel between the years 2011-2021.

Methods: This was a retrospective cohort study based on data from the Israeli National Trauma Registry (INTR).

Young-Onset Cancers-Early Steps in the Right Direction.

The global incidence of young-onset (YO) cancer is on the rise [...

Early-Onset Cancer in the Gastrointestinal Tract Is on the Rise-Evidence and Implications.

Unlabelled: Epidemiologic data indicate a significant increase in the incidence of colorectal cancer in younger populations in the past three decades. Moreover, recent evidence also demonstrates a similar trend in gastric, pancreatic, and biliary tract cancers. A majority of these early-onset cases are sporadic and lack hereditary or familial background, implying a potential key role for behavioral, lifestyle, nutritional, microbial, and environmental factors.

Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism.

Excitatory-inhibitory (E/I) imbalance is a mechanism that underlies autism spectrum disorder, but it is not systematically tested for pain processing. We hypothesized that the pain modulation profile (PMP) in autistic individuals is characterized by less efficient inhibitory processes together with a facilitative state, indicative of a pronociceptive PMP. Fifty-two adults diagnosed with autism and 52 healthy subjects, age matched and sex matched, underwent quantitative sensory testing to assess the function of the (1) pain facilitatory responses to phasic, repetitive, and tonic heat pain stimuli and (2) pain inhibitory processes of habituation and conditioned pain modulation.

Somapacitan in children born small for gestational age: a multi-centre, open-label, controlled phase 2 study.

Objective: Investigate efficacy, safety, and tolerability of 3 once-weekly somapacitan doses compared with daily growth hormone (GH) administration in short children born small for gestational age (SGA).

Design: Randomised, multi-centre, open-label, controlled phase 2 study comprising a 26-week main phase and a 4-year extension (NCT03878446). The study was conducted at 38 sites across 12 countries.

Outcomes of basic versus advanced prehospital life support in severe pediatric trauma.

Objective: The role of basic life support (BLS) vs. advanced life support (ALS) in pediatric trauma is controversial. Although ALS is widely accepted as the gold standard, previous studies have found no advantage of ALS over BLS care in adult trauma.

Knowledge and emotional attitudes of health care practitioners regarding patients with psychogenic nonepileptic seizures.

Background: Psychogenic nonepileptic seizures (PNESs) are paroxysmal events that resemble epileptic seizures without concomitant changes in electroencephalograms (EEGs) or any other physiological cause. These seizures are one of the most common and dramatic conversion disorders. First responders treat many PNES patients with unnecessary emergency abortive medication and sometimes even intubate them.

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls.

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC.

Trikafta-Extending Its Success to Less Common Mutations.

Cystic Fibrosis (a genetic recessive disease) is caused by a mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene that causes an absence of, or impaired CFTR activity [...

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review.

Background And Objective: Surgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, "curable" disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively.