Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre- and postnatal development in the cynomolgus monkey following administration of ABT-874, a human anti-IL-12/23p40 monoclonal antibody.

BACKGROUND ABT-874 is an anti-IL-12/23 monoclonal antibody that binds to the p40 subunit of human IL-12 and IL-23. As part of its preclinical safety assessment, studies were conducted to assess its potential effects on pre- and postnatal development in cynomolgus monkeys. METHODS In the embryo-fetal development studies, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 0, 5, 25, or 100 mg/kg during gestation days (GD) 20 to 48. Fetuses were examined for external, visceral, and skeletal development on GD 100 or 150. In the pre- and postnatal study, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 10, 50, or 200 mg/kg from GD 20 through postpartum day 182. Infants were examined from birth up to 9 months of age for morphological and functional development. Potential effects on the infant immune system were evaluated by immunophenotyping of peripheral blood lymphocytes and by T-dependent antibody response to KLH. RESULTS There was no ABT-874-related maternal toxicity or adverse effects on fetuses or infants. ABT-874 was present in maternal and fetal serum at GD 100 and 150, and in infant serum through day 63 postbirth. ABT-874 was also present at low levels in breast milk through postpartum day 175. CONCLUSIONS Exposure of cynomolgus monkey fetuses and infants to ABT-874 had no adverse effects on embryo-fetal or postnatal development.
The inhibin B (InhB) response to the testicular toxicants mono-2-ethylhexyl phthalate (MEHP), 1,3 dinitrobenzene (DNB), or carbendazim (CBZ) following short-term repeat dosing in the male rat.

OBJECTIVE The objective of this study was to evaluate the utility of plasma Inhibin B (InhB) as a biomarker of testicular injury in adult rats following short-term exposure to the known Sertoli cell toxicants mono-2-ethylhexyl phthalate (MEHP), 1,3 dinitrobenzene (DNB), or carbendazim (CBZ). METHODS Following oral gavage administration of the compounds for 2 or 7 days, the rats were evaluated for clinical signs, body weight, food consumption, organ weights, plasma hormone levels, and gross and microscopic pathology. RESULTS MEHP, DNB, and CBZ produced a range of testicular toxicity characterized by minimal exfoliation of germ cells as demonstrated by increased cellular debris in the epididymis (MEHP) to more severe and dose/duration responsive Sertoli cell vacuolation, germ cell degeneration, and multinucleated giant cells of germ cell origin (DNB and CBZ). The slight to moderate Sertoli and germinal cell injuries did not correlate with significant changes in plasma InhB levels following 2- or 7-day exposures. However, more severe injury to germinal epithelium following up to 7 days of exposure, but not after 2 days of exposure, correlated with decreased plasma InhB levels and less consistently with increases in plasma follicle stimulating hormone. CONCLUSION In conclusion, under the conditions of these studies, changes in InhB were not an effective early onset marker of testicular toxicity or an effective marker for slight to moderate levels of acute injury, and only reflected more severe disruption of spermatogenesis. Changes in plasma InhB and follicle stimulating hormone were poorly correlated except in some instances of moderate to marked testicular toxicity.
Epidemiology of colorectal cancer in Asia

The prevalence of colorectal cancer is increasing in Asia. However, the age‐standardized rate has reached a plateau in some countries. Some studies have shown a male predominance difference and increasing risk in the elderly, but not in the younger population. ‘Right shifting’ of colorectal cancer, not accountable by difference in age or the indications for endoscopic examination, has also been noted. Westernized diet is associated with colorectal cancer, but controversy remains on how it causes colorectal cancer. Alcohol consumption, obesity, diabetes mellitus, consumption of red and processed meat and cigarette smoking are linked to bowel cancer epidemiologically. Only high dietary calcium has a consistent negative (or ‘protective’) effect. The efficacy of fish oil, vitamin D, soy, phytoestrogens, folate, methionine, riboflavin and vitamin B6 has not been established. Aspirin and non‐steroidal anti‐inflammatory drugs use decrease risk of colorectal cancer after 5–10 years of use. There is no evidence for a detrimental effect of proton pump inhibitors or benefit of statins in colorectal cancer. In conclusion, there is a rising trend and prevalence of colorectal cancer in Asia. Dietary modification or supplementation may not be effective in preventing colorectal cancer. Surveillance of colorectal cancer in high‐risk groups, according to current recommendation, is probably most effective.
Confidence in newly qualified midwives

This article focuses on the level of confidence in students exiting from three pre-registration programmes leading to a midwifery qualification. Confidence was explored using a tool covering 24 basic skills. This was given to students from 18-month, 3-year and 4-year courses on the last day of their course. A total of 45 responded. Results were analyzed using descriptive statistics. Generally all scores were similar from 18-month and 4-year students but this may have occurred because of curriculum similarities. Three-year students showed a wider variation of confidence levels in all skills. Multiple factors play a part in developing confidence, including the quality of the learning experience, the educational programme and personality. These need further exploration.
Evidence for a critical role of ceruloplasmin oxidase activity in iron metabolism of Wilson disease gene knockout mice

Background and Aim: Wilson disease is a genetic disorder associated with copper overload due to mutations within the ATP7B gene. Although copper and iron metabolism are closely linked, the influence of mutations of the ATP7B gene on iron homeostasis is unknown. Therefore, the present study was carried out to elucidate iron metabolism in Atp7b(−/−) mice, an animal model of Wilson disease.
Second stage of labor and epidural use: a larger effect than previously suggested.

robotic sacrocolpopexy and one commentary. The randomized trial provides no new insights on the would-be superiority of robotic surgery on outcomes such as comorbidity or effectiveness. What is more, costs of robotic surgery were significantly higher and patient pain scores 1 week after surgery were higher in the robotics group. These findings are consistent with previous studies. As Dr. Advincula rightly mentions, cost analyses are difficult to perform. In our view, however, costs of ergonomic circumstances and physical challenges of (conventional) minimally invasive surgery must also be taken into account. These include both direct costs for the health care provider and indirect costs (ie, from the hospital or societal perspective). First, it is generally known that laparoscopic surgery imposes a high risk of physical complaints and injuries among surgeons. Among our directly known colleagues performing minimally invasive surgery, there are cases of cervical and lumbar hernias, frozen shoulders, and finger compression neuropathies. Physical strain rates up to 88% of gynecologists who perform minimally invasive surgery have been described. By illustration, in the study by Franasiak et al, 29% of gynecologists had therapy, such as physical therapy, because of minimally invasive surgery–related physical discomfort or even took time off. Second, to decrease pain, surgeons limited the number of minimally invasive surgery procedures per day or limited the total number of cases. Third, data from large disability insurance companies reveal that surgeons performing minimally invasive surgery have a relative risk of 2–3 of becoming unfit for work during their careers compared with medical doctors not performing minimally invasive surgery (courtesy of MOVIR, Health Insurance Company in The Netherlands). Considering the aforementioned conditions, a complete cost analysis of robotic surgery ideally would include all expenses, both direct and indirect. We realize that, until now, it has been rather unusual to include expenses from the surgeon’s point of view. Nevertheless, to achieve a comprehensive analysis of all benefits and risks regarding robotic surgery in gynecology, ergonomics-related aspects and, in particular, cost items also should be included.
In reply.

others, that the duration of the second stage of labor is positively correlated with insult to the pelvic floor. We showed that, when the second stage of labor exceeds 90 minutes, the risk of pelvic floor injury doubles; when the second stage exceeds 160 minutes, the risk reaches a frightening level of 3.5. We and many others have recognized the importance of protecting the pelvic floor during parturition as a public health goal for long-term quality of life. Longevity will further exponentially affect the prevalence of women suffering from various degrees of pelvic floor dysfunction requiring surgical repair. We do not agree that there is any justification to implement new, longer norms for the duration of the second stage of labor; rather, treatment guidelines should be developed for limiting secondstage duration aimed at protecting the well-being of both neonates and mothers.
A Revised Birth Weight Reference for the United States

OBJECTIVE: To generate birth weight curves based on the obstetric estimate of gestational age as specified in the revised 2003 U.S. birth certificate. METHODS: Using National Center for Health Statistics data from 2011, we constructed birth weight curves for neonates between 24 and 42 weeks of gestation. Curves were developed using the obstetric estimate of gestational age that is included in the revised 2003 U.S. birth certificate, which, when available, incorporates ultrasound dating information. Live-born singleton neonates between 500 and 6,000 g without malformations were included. These curves were compared with curves we generated using 1991 data on which the current national reference of Alexander and colleagues is based, a reference that used only last menstrual period to establish gestational age. RESULTS: The 1991 curves were based on 3,684,778 U.S. live births and the 2011 on 3,252,011 births. Birth weight percentile values were greater from 28 to 36 weeks of gestation in the 1991 data set. That is, the birth weights for preterm neonates were overestimated when 1991 reference curves were used compared with the proposed 2011 reference. For example, in 1991, a birth weight of 2,000 g was at the 50th percentile between 31 and 32 weeks of gestation, whereas in 2011, a birth weight of 2,000 g now corresponds to the 50th percentile between 33 and 34 weeks of gestation. CONCLUSIONS: Our revised reference curve for the United States provides an updated national reference for birth weight. LEVEL OF EVIDENCE: II
Management of Multiple Sclerosis During Pregnancy and the Reproductive Years: A Systematic Review

OBJECTIVE: To examine the evidence guiding management of multiple sclerosis (MS) in reproductive-aged women. DATA SOURCES: We conducted an electronic literature search using PubMed, ClinicalTrials.gov, and other available resources. The following keywords were used: “multiple sclerosis” and “pregnancy. ” We manually searched the reference lists of identified studies. METHODS OF STUDY SELECTION: Two reviewers categorized all studies identified in the search by management topic, including effect of pregnancy on MS course, fetal risks associated with disease-modifying treatments during pregnancy, and management of patients off disease-modifying treatment. We categorized studies by strength of evidence and included prior meta-analyses and systematic studies. These studies were then summarized and discussed by an expert multidisciplinary team. TABULATION, INTEGRATION, AND RESULTS: The risk of MS relapses is decreased during pregnancy and increased postpartum. Data are lacking regarding the risks of disease-modifying treatments during pregnancy. There may be an increased risk of MS relapses after use of assisted reproductive techniques. There does not appear to be a major increase in adverse outcomes in newborns of mothers with MS. CONCLUSION: Although there are many unmet research needs, the reviewed data support the conclusion that in the majority of cases, women with MS can safely choose to become pregnant, give birth, and breastfeed children. Clinical management should be individualized to optimize both the mother's reproductive outcomes and MS course.
Significance of each narrow‐band imaging finding in diagnosing squamous mucosal high‐grade neoplasia of the esophagus

Background and Aim: Although narrow‐band imaging (NBI) is used increasingly in clinical situations, the significance of each NBI finding has not been investigated. The primary endpoint of the present study was to identify the significant NBI findings to diagnose esophageal mucosal high‐grade neoplasia.
Dentine hypersensitivity: Simple steps for everyday diagnosis and management

It is generally accepted that dentine hypersensitivity is among the most common painful conditions affecting oral comfort and function. With regard to the aetiology, dentine hypersensitivity represents a symptom of presumably multi-factorial pathology consisting mainly of abfractive, abrasive, or erosive components (or a combination). Primary treatment strategies should undoubtedly aim at eliminating these pre-disposing factors, thus preventing recurrence of the condition; for ready alleviation of mild or moderate symptoms, occlusion of dentinal tubules (opened mainly by erosion) can be non-invasively achieved by using desensitising toothpastes containing strontium salts and/or highly concentrated fluoride lacquers or varnishes. A second approach is to use potassium salt formulations modulating intradental nerve excitability. In cases of pronounced severity a (semi-) invasive therapy should be preferred by blocking the dentinal tubules with bonding agents or adhesive restorative materials.
Clinical clues to suspicion of IgG4‐associated sclerosing cholangitis disguised as primary sclerosing cholangitis or hilar cholangiocarcinoma

Background and Aim: This study aimed to determine the clinical characteristics of immunoglobulin G4 (IgG4)‐associated sclerosing cholangitis (ISC) and provide clinical clues differentiating ISC from primary sclerosing cholangitis (PSC) or hilar cholangiocarcinoma (CCC).
Interleukin‐1B and interleukin‐1 RN polymorphisms and gastric carcinoma risk: A meta‐analysis

Background and Aim: We aimed to explore the role of interleukin (IL)‐1B cluster gene polymorphisms at positions −511, −31, and +3954 and the receptor IL‐1RN variable number tandem repeat polymorphisms in the susceptibility to gastric carcinoma through a systematic review and meta‐analysis.
Omega-3 Long Chain Polyunsaturated Fatty Acids to Prevent Preterm Birth: A Systematic Review and Meta-analysis

OBJECTIVE: To evaluate the efficacy of omega-3 in reducing the incidence of preterm birth. DATA SOURCES: Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords related to “fish oil,” “pregnancy,” and “omega-3. ” METHODS OF STUDY SELECTION: We included all randomized controlled trials of asymptomatic women with singleton gestations who were randomized to prophylactic treatment with either omega-3 supplementation or control (either placebo or no treatment). Exclusion criteria included trials in women with multiple gestations, intrauterine growth restriction, gestational hypertension or preeclampsia at randomization, prior preterm birth, and trials with polyunsaturated fatty acids as control. TABULATION, INTEGRATION, AND RESULTS: Nine randomized trials including 3,854 eligible women were identified. Women who received omega-3 had a similar rate of preterm birth before 37 weeks of gestation compared with women in the control group (7.7% compared with 9.1%, respectively; relative risk 0.90, 95% confidence interval [CI] 0.72–1.11). There were no significant differences in birth weight, neonatal intensive care unit admission, necrotizing enterocolitis, sepsis, or perinatal death in the omega-3 compared with control groups, respectively. There were no significant differences in the subgroup analyses, except for the rate of perinatal death, which was lower (0.3% compared with 1.2%; relative risk 0.27, 95% CI 0.09–0.80) in the women who received omega-3 before 21 weeks of gestation and in trials with low risk of bias (0.3% compared with 1.0%; relative risk 0.28, 95% CI 0.09–0.89) compared with women in the control group. However, in no randomized controlled trial was perinatal death the primary outcome. CONCLUSION: Omega-3 supplementation during pregnancy does not reduce the incidence of preterm birth or improve neonatal outcome.
Tentativa de avaliação do programa especial de controle da esquistossomose (PECE) no Estado da Paraíba, Brasil

An attempt was made to evaluate the efficacy of the Special Programme for Schistosomiasis Control (PECE) carried out in the state of Paraiba since 1976 by Superintendencia das Campanhas de Saude Publica (SUCAM), Ministry of Health of Brazil. The evaluation was based on five stool examinations done by SUCAM in the school children of the endemic area from 1978 to 1983 and on a clinical and quantitative stool examination performed in 1984 and 1985 in a sample of 9155 persons living in three selected municipalities each one in a different region of the endemic area: Mamanguape, Paraiba and Litoral Sul. The stool examinations performed from 1978 to 1983 showed a drop of S. mansoni infection from 28% to 4.9% in Mamanguape, 20.9% to 5.9% in Paraiba 40.2% to 18.9% in Litoral Sul and 4.9% to 1.4% in Curimatau. At the local level, however, the prevalence of the infection in 1983 was 20% or higher in 36(10.9%) of329 localities evaluated in Mamanguape, 40 (13.6%) of293 in Paraiba and 43(47.2%) of 91 localities of Litoral Sul. The sample of the population submitted to clinical and a quantitative stool examination showed 4.4% passing an average of 123 eggs of S. mansoni per gram of feces in Mamanguape where 12.9% of the positive cases had a palpable liver and none had the hepatosplenic form of the disease. In Paraiba 10.9% of the sample was positive for S. mansoni, with an average of 165.9 eggs per gram offices; 11.7% of the positives had a palpable liver and only one (0.24%) had the hepatosplenic form. In Litoral Sul 24.5% of the sample passed an average of 115.4 eggs per gram of feces, 17.1% of the positives had a palpable liver and 3.6% had the hepatosplenic form of the disease. The authors conclude that the programme was able to reduce the prevalence of the infection and possibly to reduce the morbidity of the disease in Mamanguape, Paraiba and Curimatau, but was less efficient in reducing the prevalence of infection and unable to reduce the morbidity of the disease in the population of Litoral Sul.
Hepatitis E: Historical, contemporary and future perspectives

Hepatitis E was suspected for the first time in 1980 during a waterborne epidemic of acute hepatitis in Kashmir, India. In the 30 years since then, a small virus with single‐stranded RNA genome has been identified as the cause of this disease and named as hepatitis E virus (HEV). The virus has four genotypes; of these, genotypes 1 and 2 are known to infect only humans, whereas genotypes 3 and 4 primarily infect other mammals, particularly pigs, but occasionally cause human disease. In highly‐endemic areas, the disease occurs in epidemic and sporadic forms, caused mainly by infection with genotype 1 or 2 virus, acquired through the fecal‐oral route, usually through contaminated water supplies. The disease is characterized by particularly severe course and high mortality among pregnant women. In persons with pre‐existing chronic liver disease, HEV superinfection can present as acute‐on‐chronic liver disease. In low‐endemic regions, sporadic cases of locally‐acquired HEV infection are reported; these are caused mainly by genotype 3 or 4 HEV acquired possibly through zoonotic transmission from pigs, wild boars or deer. In these areas, chronic infection with genotype 3 HEV, which may progress to liver cirrhosis, has been reported among immunosuppressed persons. Two subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in preventing the disease; however, these are not yet commercially available. These vaccines should be of particular use in groups that are at high risk of HEV infection and/or of poor outcome.
A review of the efficacy of the dopamine agonists pergolide and bromocriptine in the treatment of Parkinson's disease

This review summarizes those studies, completed over the last 15 years, which compare the clinical benefit of the two most commonly used dopamine agonists, pergolide and bromocriptine. In these studies, both drugs were evaluated as adjunctive therapy to levodopa for the treatment of Parkinson's disease (PD). Ten studies are analyzed and the affect of pergolide and bromocriptine on PD compared. Although variation in study design and disease rating scales prevents the opportunity for a true meta‐analysis, this review analyses the outcome of each individual study to assess the benefit of pergolide over bromocriptine. Pergolide improves patients' activities‐of‐daily‐living and their clinical PD symptoms over bromocriptine. Additionally, a large percentage of patients who do not respond to bromocriptine, or whose PD symptoms worsened, improved on pergolide. Furthermore, patients who are adequately treated with bromocriptine experienced additional improvement with pergolide therapy. In summary, pergolide provided benefits to PD patients over bromocriptine in nine studies and was equivalent in the tenth. The benefits associated with pergolide may be partly due to the action of pergolide on dopamine D1 and D2 receptors (bromocriptine is associated with the D2 agonism). In conclusion, in the majority of completed studies to date, pergolide provided greater improvement to the clinical signs and symptoms of PD than bromocriptine.