Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of Odor-Receptor Pairs in Caenorhabditis elegans Reveals Different Receptors for High and Low Odor Concentrations

Distinct receptors and neuronal circuits enable worms to move toward low and away from high concentrations of the same chemical. Detecting Too Much of a Good Thing Worms, such as the nematode Caenorhabditis elegans, rely on chemosensory perception to move toward nutrient sources and away from noxious chemicals. However, some chemicals are beneficial at low concentrations but hazardous at high concentrations. Taniguchi et al. used an RNA interference screen to match several odorant molecules to genes encoding 194 G protein–coupled receptors, creating a useful launching point for studying chemosensory perception signaling. C. elegans used different receptors in different neurons to respond to high or low concentrations of diacetyl, a chemical that attracts worms at low concentrations and repulses them at high concentrations. Olfactory systems sense and respond to various odorants. Olfactory receptors, which in most organisms are G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors, directly bind volatile or soluble odorants. Compared to the genomes of mammals, the genome of the nematode Caenorhabditis elegans contains more putative olfactory receptor genes, suggesting that in nematodes there may be combinatorial complexity to the receptor-odor relationship. We used RNA interference (RNAi) screening to identify nematode olfactory receptors necessary for the response to specific odorants. This screening identified 194 candidate olfactory receptor genes linked to 11 odorants. Additionally, we identified SRI-14 as being involved in sensing high concentrations of diacetyl. Rescue and neuron-specific RNAi experiments demonstrated that SRI-14 functioned in ASH neurons, specific chemosensory neurons, resulting in avoidance responses. Calcium imaging revealed that ASH neurons responded to high diacetyl concentrations only, whereas another class of chemosensory neurons, AWA neurons, reacted to both low and high concentrations. Loss of SRI-14 function hampered ASH responses to high diacetyl concentrations, whereas loss of ODR-10 function reduced AWA responses to low odorant concentrations. Chemosensory neurons ectopically expressing SRI-14 responded to a high concentration of diacetyl. Thus, nematodes have concentration-dependent odor-sensing mechanisms that are segregated at the olfactory receptor and sensory neuron levels.
Dancers with achilles tendinopathy demonstrate altered lower extremity takeoff kinematics.

STUDY DESIGN Controlled laboratory study using a cross-sectional design. OBJECTIVES To analyze lower extremity kinematics during takeoff of a "saut de chat" (leap) in dancers with and without a history of Achilles tendinopathy (AT). We hypothesized that dancers with AT would demonstrate different kinematic strategies compared to dancers without pathology, and that these differences would be prominent in the transverse and frontal planes. BACKGROUND AT is a common injury experienced by dancers. Dance leaps such as the saut de chat place a large demand on the Achilles tendon. METHODS Sixteen female dancers with and without a history of AT (mean ± SD age, 18.8 ± 1.2 years) participated. Three-dimensional kinematics at the hip, knee, and ankle were quantified for the takeoff of the saut de chat, using a motion analysis system. A force platform was used to determine braking and push-off phases of takeoff. Peak sagittal, frontal, and transverse plane joint positions during the braking and push-off phases of the takeoff were examined statistically. Independent samples t tests were used to evaluate group differences (α = .05). RESULTS The dancers in the tendinopathy group demonstrated significantly higher peak hip adduction during the braking phase of takeoff (mean ± SD, 13.5° ± 6.1° versus 7.7° ± 4.2°; P = .046). During the push-off phase, dancers with AT demonstrated significantly more internal rotation at the knee (13.2° ± 5.2° versus 6.9° ± 4.9°; P = .024). CONCLUSION Dancers with AT demonstrate increased peak transverse and frontal plane kinematics when performing the takeoff of a saut de chat. These larger displacements may be either causative or compensatory factors in the development of AT.
Early Low‐Grade Proteinuria: Causes, Short‐Term Evolution and Long‐Term Consequences in Renal Transplantation

Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low‐grade (<1 g/24 h) proteinuria earlier after transplantation and its short‐term change affect long‐term graft survival. The effects of proteinuria and its change on long‐term graft survival were retrospectively assessed in 484 renal transplant recipients. One‐ and 3‐month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One‐ and 3‐month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p < 0.0001)—especially low‐grade proteinuria (HR: 1.20 and 1.26, p < 0.0001)—were powerful, independent predictors of graft loss. Its short‐term reduction correlated with arterial pressure (AP) (the lower the 3‐month diastolic and 12‐month systolic AP, the lower the risk of increasing proteinuria during 1–3 months and 3–12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p = 0.01 and 0.85, respectively, p = 0.02), and was associated with decreased long‐term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p < 0.0001), independently of initial proteinuria. Early low‐grade proteinuria due to pre‐transplant renal lesions, ischemia‐reperfusion and immunologic injuries is a potent predictor of graft loss. Short‐term reduction in proteinuria is associated with improved long‐term graft survival.
Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: correlation with microvessel density and clinicopathologic features.

Angiogenesis, a process related to tumor growth and malignancy, is stimulated by several growth factors. Among these is vascular endothelial growth factor (VEGF), which acts on endothelial cells by binding with 2 specific receptors, VEGFR1 and VEGFR2. Recent studies have demonstrated that VEGF expression is correlated with microvessel density (MVD) and tumor progression. Digestive endocrine tumors are heterogeneous neoplasms exhibiting variable biological aggressiveness and behavior that often are not predictable on morphologic grounds alone. The aims of this study were to evaluate the expression of VEGF, VEGFR1, and VEGFR2 in digestive endocrine tumors and to examine its correlation with MVD and malignancy. A total of 84 specimens from endocrine neoplasms and normal gut and pancreatic tissue were immunohistochemically studied using specific antibodies directed against VEGF, VEGFR1, VEGFR2, endothelial antigens, and gastroenteropancreatic hormones. Ultrastructural immunocytochemistry was performed to identify the cellular localization of VEGF and the VEGFRs. In normal tissues, VEGF immunoreactivity was detected in G cells and PP cells. Ultrastructurally, VEGF was localized within secretory granules. The VEGFRs were not significantly expressed by normal endocrine cells. VEGF-immunoreactive (IR) cells were detected in 40 of 83 tumors, mainly G cell and enterochromaffin cell neoplasms. VEGFR1-IR cells were found in 44 of 82 tumors, and VEGFR2-IR cells were found in 55 of 82 tumors, with no predilection for any specific tumor type. The expression of VEGF and its receptors did not correlate with MVD or malignancy. These results suggest that in normal tissues, endothelial functions may be regulated by VEGF produced by some endocrine cells and that a VEGF/VEGFR binding mechanism may be involved in tumorigenesis, but not in tumor progression and aggressiveness.
Relationship Between Dental Panoramic Radiographic Findings and Biochemical Markers of Bone Turnover

We investigated whether mandibular cortical measures on dental panoramic radiographs are associated with biochemical markers of bone turnover in 82 postmenopausal women. Mandibular cortical shape was significantly associated with biochemical markers and spinal BMD. Our results suggest that dentists may be able to identify postmenopausal women with low BMD by using dental panoramic radiographs.
The relationship between oral tori and bite force

Abstract Objective The relationship between bite force and torus palatinus or mandibularis remains to be explained. The major aim of this study was to determine the correlation between bite force and oral tori. Methods The bite force of 345 patients was measured with a bite force recorder; impressions of the shape and size of the oral tori were taken on plaster models prior to orthodontic treatments. Subsequently, the relationship between oral tori and bite force was analyzed. Results The size, shape, and incidence of torus palatinus was not significantly correlated with bite force. However, the size of torus mandibularis increased significantly in proportion to the bite force (p = 0.020). The occurrence of different types of oral tori was not correlated with the bite force. Discussion The size of torus mandibularis provides information about bite force and can thus be used to clinically assess occlusal stress.
Specific interaction of the yeast cis-Golgi syntaxin Sed5p and the coat protein complex II component Sec24p of endoplasmic reticulum-derived transport vesicles.

The generation of transport vesicles at the endoplasmic reticulum (ER) depends on cytosolic proteins, which, in the form of subcomplexes (Sec23p/Sec24p; Sec13p/Sec31p) are recruited to the ER membrane by GTP-bound Sar1p and form the coat protein complex II (COPII). Using affinity chromatography and two-hybrid analyses, we found that the essential COPII component Sec24p, but not Sec23p, binds to the cis-Golgi syntaxin Sed5p. Sec24p/Sed5p interaction in vitro was not dependent on the presence of [Sar1p.GTP]. The binding of Sec24p to Sed5p is specific; none of the other seven yeast syntaxins bound to this COPII component. Whereas the interaction site of Sec23p is within the N-terminal half of the 926-aa-long Sec24p (amino acid residues 56-549), Sed5p binds to the N- and C-terminal halves of the protein. Destruction by mutagenesis of a potential zinc finger within the N-terminal half of Sec24p led to a nonfunctional protein that was still able to bind Sec23p and Sed5p. Sec24p/Sed5p binding might be relevant for cargo selection during transport-vesicle formation and/or for vesicle targeting to the cis-Golgi.
Spasticity: The Misunderstood Part of the Upper Motor Neuron Syndrome

Ivanhoe CB, Reistetter TA: Spasticity: The misunderstood part of the upper motor neuron syndrome. Am J Phys Med Rehabil 2004;83(suppl):S3–S9. Spasticity is a sensorimotor phenomenon related to the integration of the nervous system motor responses to sensory input. Although most commonly considered a velocity-dependent increase to tonic stretch, it is related to hypersensitivity of the reflex arc and changes that occur within the central nervous system, most notably, the spinal cord. Injury to the central nervous system results in loss of descending inhibition, allowing for the clinical manifestation of abnormal impulses. Muscle activity becomes overactive. This is mediated at several areas of the stretch-reflex pathway. Although spasticity is part of the upper motor neuron syndrome, it is frequently tied to the other presentations of the said syndrome. Contracture, hypertonia, weakness, and movement disorders can all coexist as a result of the upper motor neuron syndrome. Although basic science descriptions of spasticity are being elucidated, clinically, confusion exists.
Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms.

PURPOSE To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.
Economic Empowerment of Impoverished IPV Survivors

Best practices in advocating for economic empowerment of impoverished intimate partner violence (IPV) survivors require the comprehensive and holistic organization of program and service delivery systems. This article outlines the best practices literature that addresses IPV in the lives of impoverished women, as well as the literature that specifically examines the interventions to economically empower IPV survivors—whether impoverished or not. This article concludes with suggestions for policy makers on how to incorporate these best practices into the Violence Against Women Act and for practitioners to ensure a comprehensive approach to interventions for impoverished IPV survivors.
Primary extraskeletal myxoid chondrosarcoma of the vulva

Primary extraskeletal myxoid chondrosarcoma (EMC) of the vulva is extremely rare. There is little available information about the biological behavior and treatment strategy for primary EMC of the vulva. We report a rare case of primary EMC of the vulva treated surgically. A 24‐year‐old Japanese woman had demonstrated a small and elastic mass of the vulva and underwent enucleation of the mass at a previous hospital, but a definitive histopathological diagnosis was not obtained. Therefore, the patient was referred to our hospital for further evaluation and treatment. We histopathologically diagnosed the tumor as primary EMC of the vulva and performed vulvectomy with vulvoperineal reconstruction. Microscopic examination of the resected specimens demonstrated residual tumor nodules of EMC. However, there were no viable tumor cells at the surgical margin. Approximately two years after wide local excision was performed, the patient is doing well and there is no apparent recurrence of EMC.
RESEARCH ARTICLE: Neurogenesis Impairment and Increased Cell Death Reduce Total Neuron Number in the Hippocampal Region of Fetuses with Down Syndrome

We previously obtained evidence for reduced cell proliferation in the dentate gyrus (DG) of fetuses with Down syndrome (DS), suggesting that the hippocampal hypoplasia seen in adulthood may be caused by defective early neuron production. The goal of this study was to establish whether DS fetuses (17–21 weeks of gestation) exhibit reduction in total cell number in the DG, hippocampus and parahippocampal gyrus (PHG). Volumes of the cellular layers and cell number were estimated with Cavalieri's principle and the optical fractionator method, respectively. We found that in DS fetuses all investigated structures had a reduced volume and cell number. Analysis of cell phenotype showed that DS fetuses had a higher percentage of cells with astrocytic phenotype but a smaller percentage of cells with neuronal phenotype. Immunohistochemistry for Ki‐67, a marker of cycling cells, showed that DS fetuses had less proliferating cells in the germinal zones of the hippocampus and PHG. We additionally found that in the hippocampal region of DS fetuses there was a higher incidence of apoptotic cell death. Results show reduced neuron number in the DS hippocampal region and suggest that this defect is caused by disruption of neurogenesis and apoptosis, two fundamental processes underlying brain building.
Next-generation tumor profiling identified high total mutation burden (TMB) in Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB): A potential rationale for Immunotherapy

Urinary Bladder Cancer (BC) is a heterogeneous disease with diverse morphologic and clinical manifestations. Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is rare form of BC with no standard therapies. Thus, novel therapies based on underlying tumor biology are needed. Molecular profiling can be used to detect mutational load and molecular subtypes of tumors, which may help in predicting a patient’s sensitivity to immunotherapy approaches, such as PD-1/PD-L1 inhibition. Here we present a case of Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) in a 67-year-old male who underwent transurethral resection of bladder tumor (TURBT), pathology revealed muscle-invasive urothelial carcinoma, lymph epithelial type. Next-generation gene sequencing identified multiple gene alterations, and high Total Mutation Burden (TMB) in tumor specimens, suggesting targeting the PD-1/PD-L1 axis may be a therapeutic option. A further characterization and description of the outcomes of these rare tumors is warranted to help guide physicians and counsel patients. *Corresponding author: Jue Wang, M.D., Professor of Medicine Director of Genitourinary Oncology Section University of Arizona Cancer Center at Dignity Health St. Joseph’s, Phoenix, AZ 625 N 6th Street, Phoenix, AZ 85004, Tel: +1 602-406-8222; E-mail: jue.wang@dignityhealth.org
Phylogenetic Composition of Arctic Ocean Archaeal Assemblages and Comparison with Antarctic Assemblages

ABSTRACT Archaea assemblages from the Arctic Ocean and Antarctic waters were compared by PCR-denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA genes amplified using the Archaea-specific primers 344f and 517r. Inspection of the DGGE fingerprints of 33 samples from the Arctic Ocean (from SCICEX submarine cruises in 1995, 1996, and 1997) and 7 Antarctic samples from Gerlache Strait and Dallman Bay revealed that the richness of Archaea assemblages was greater in samples from deep water than in those from the upper water column in both polar oceans. DGGE banding patterns suggested that most of the Archaea ribotypes were common to both the Arctic Ocean and the Antarctic Ocean. However, some of the Euryarchaeota ribotypes were unique to each system. Cluster analysis of DGGE fingerprints revealed no seasonal variation but supported depth-related differences in the composition of the Arctic Ocean Archaea assemblage. The phylogenetic composition of the Archaea assemblage was determined by cloning and then sequencing amplicons obtained from the Archaea-specific primers 21f and 958r. Sequences of 198 clones from nine samples covering three seasons and all depths grouped with marine group I Crenarchaeota (111 clones), marine group II Euryarchaeota (86 clones), and group IV Euryarchaeota (1 clone). A sequence obtained only from a DGGE band was similar to those of the marine group III Euryarchaeota.
No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths.

OBJECTIVE Fewer than 3% of 4 million annual neonatal deaths occur in countries with reliable vital registration (VR) data. Global estimates for asphyxia-related neonatal deaths vary from 0.7 to 1.2 million. Estimates for intrapartum stillbirths are not available. We aimed to estimate the numbers of intrapartum-related neonatal deaths and intrapartum stillbirths in the year 2000. METHODS Sources of data on neonatal death included: vital registration (VR) data on neonatal death from countries with full (> 90%) VR coverage (48 countries, n = 97,297); studies identified through literature searches (> 4000 abstracts) and meeting inclusion criteria (46 populations, 30 countries, n = 12,355). A regression model was fitted to cause-specific proportionate mortality data from VR and the literature. Predicted cause-specific proportions were applied to the number of neonatal deaths by country, and summed to a global total. Intrapartum stillbirths were estimated using median cause-specific mortality rate by country (73 populations, 52 countries, n = 46,779) or the subregional median in the absence of country data. FINDINGS Intrapartum-related neonatal deaths were estimated at 0.904 million (uncertainty 0.65-1.17), equivalent to 23% of the global total of 4 million neonatal deaths. Country-level model predictions compared well with population-based data sets not included in the input data. An estimated 1.02 million intrapartum stillbirths (0.66-1.48 million) occur annually, comprising 26% of global stillbirths. CONCLUSION Intrapartum-related neonatal deaths account for almost 10% of deaths in children aged under 5 years. Intrapartum stillbirths are a huge and invisible problem, but are potentially preventable. Programmatic attention and improved information are required.
Endogenous Endotoxin Participates in Causing a Panenteric Inflammatory Ileus After Colonic Surgery

Objective:To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus. Background:Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction. Methods:Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath. Results:Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42% compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction. Conclusions:Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.