Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in the use of cell penetrating peptides for respiratory drug delivery

ABSTRACT Introduction Respiratory diseases are leading causes of death in the world, still inhalation therapies are the largest fail in drug development. There is an evident need to develop new therapies. Biomolecules represent apotential therapeutic agent in this regard, however their translation to the clinic is hindered by the lack of tools to efficiently deliver molecules. Cell penetrating peptides (CPPs) have arisen as apotential strategy for intracellular delivery that could theoretically enable the translation of new therapies. Areas covered In this review, the use of CPPs as astrategy to deliver different molecules (cargoes) to treat lung-relateddiseases will be the focus. Abrief description of these molecules and the innovative methods in designing new CPPs is presented. The delivery of different cargoes (proteins, peptides, poorly soluble drugs and nucleic acids) using CPPs is discussed, focusing on benefits to treat different respiratory diseases like inflammatory disorders, cystic fibrosis and lung cancer. Expert opinion The advantages of using CPPs to deliver biomolecules and poorly soluble drugs to the lungs is evident. This field has advanced in the past few years toward targeted intracellular delivery, although further studies are needed to fully understand its potential and limitations in vitro and in vivo.
Characteristics of the Two Asian Bumblebee Species Bombus friseanus and Bombus breviceps (Hymenoptera: Apidae)

This study compared the food plants, life cycle, colony development, and mating behaviour of the two Asian bumblebee species Bombus friseanus and B. breviceps, which are very important pollinators for many wild flowers and crops in local ecosystems. Both species were shown to be highly polylectic. Differences were observed in their life cycles and colony development patterns. The colony foundation rate of the field-collected queens was high in both species, 95.5% in B. friseanus and 86.5% in B. breviceps. The intervals from colony initiation to colony sizes of 30, 60, and 80 workers and to the first male and gyne emergence were significantly shorter in B. friseanus than in B. breviceps (p < 0.01). The development period of the first batch of workers showed no significant difference between the two species (p > 0.05). Compared with B. friseanus, B. breviceps produced remarkably higher numbers of workers (135 ± 30 workers/colony in B. friseanus and 318 ± 123 workers/colony in B. breviceps) and males (199 ± 46 males/colony in B. friseanus and 355 ± 166 males/colony in B. breviceps) (p < 0.01), with notable variation was found among the colonies in both species. With no significant difference in the mating rate between these two species, the copulation duration of B. breviceps (1.54 ± 0.63 min) was strikingly shorter than that of B. friseanus (27.44 ± 11.16 min) (p < 0.001). This study highlights the characteristics of the two Asian bumblebee species and will aid further studies on their conservation and agricultural pollination use.
Influence of rohu (Labeo rohita) deboning by-product on composition, physical properties and sensorial acceptability of rohu cutlets

Purpose The purpose of the study was to utilize rohu deboning by-product to develop edible cutlets and to study its effects on quality and acceptability. Design/methodology/approach Fish cutlets were prepared with varying mince and by-product ratios (100:0, 75:25, 50:50, 25:75 and 0:100 per cent) and the effect of by-product inclusion on composition, cooking characteristics, texture and acceptability were studied. Findings Cutlets from control group had highest values for protein, fat, diameter reduction, fat retention and height increase (29.9, 14.9, 7.6, 78.3 and 31.9 per cent) compared to other lots. Highest values for cooking yield (p > 0.01), lightness and whiteness were (92.7, 35.4 and 31.2 per cent) found in cutlets from 100 per cent BP lot. Hardness and shear force increased with by-product content (p 0.01). By-products can be incorporated up to 50 per cent into fish cutlets without negatively affecting the eating quality. Research limitations/implications Amount of by-product to be added was the limitation during the work. More by-product content in the cutlets resulted in low-palatability. Total calcium content in the cutlets need to be checked as calcium content per serving should not be above the regulations. Practical/implications In general, nutritionally rich fish deboning by-product is used for cattle feeding or discarded into dumping grounds causing pollution, nutritional, as well as economic loss to the farmers. The findings of this study will be helpful to develop nutritionally rich and edible food products from this deboning by-product. Incorporation of by-product into cutlets will allow the farmers to sell their products at lower prices without compromising the profits, which will improve the marketing as well as consumption. Social/implications Utilization of fish deboning by-product to develop edible cutlets helps in reducing the operational costs, pollution and efficient utilization of process by-products. Originality/value The work is completely original in nature. The results reported are unique and the outcome of the research has social applicability.
A Young Patient with Brief Alcohol Use and Rapidly Progressive Alcohol-Related Hepatitis: Considerations in Transplant Eligibility.

History of Present Illness JD was admitted to a community hospital with abdominal pain consistent with alcohol-related hepatitis after a relapse into heavy drinking. This hospital admission was his fourth for complications of alcohol use disorder (AUD). Due to concern for bacterial peritonitis, he underwent a paracentesis that was complicated by hemoperitoneum, prompting initiation of massive transfusion and transfer to a tertiary medical center for embolization of a suspected variceal injury. Despite repeated efforts by interventional radiology, no bleeding source was localized. Even after significant blood loss, JD remained hemodynamically stable. Following massive transfusion in the ICU, he was transferred to the general medicine service. He was evaluated by a gastroenterologist, who determined that no additional treatment for alcohol-related hepatitis was likely to offer benefit. Although his Maddrey’s discriminant function at the time of initial presentation was 100, steroid treatment had initially been withheld due to concern for bacterial peritonitis. Subsequently, after infection had been ruled out by diagnostic paracentesis, steroid treatment was thought to confer no additional benefit. The only definitive treatment was liver transplantation, for which JD was ineligible due to ongoing alcohol use. On evaluation JD appeared severely cachectic. His physical examination was notable for scleral icterus, numerous spider angiomas over his back and shoulders, a tensely distended abdomen, and significant bilateral lower-extremity edema.
Epidemiological characteristics of 2019-ncoV infections in Shaanxi, China by February 8, 2020

In December 2019, a new coronavirus named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causing severe acute respiratory disease emerged in the region of Wuhan, China [1, 2]. The National Health Commission of the People's Republic of China named pneumonia infected with SARS-CoV-2 as novel coronavirus pneumonia (NCP). Evidence pointed towards person-to-person transmission [3–5]. As of 8 February 2020, China had reported 34 673 confirmed cases and more than 27 657 suspected cases of NCP across 34 Chinese provinces or municipalities, with 106 fatalities. Most of the studies focused on the epidemic situation in Wuhan, but a few studies focused on provinces outside Wuhan. Shaanxi is located to the northwest of the Hubei Province and is adjacent to it, with a population of 38.64 million. Since the first case of NCP was confirmed in Shaanxi on 23 January 2020, 195 cases have been confirmed, but there was no relevant epidemiological study. In order to better understand the epidemic of the new coronavirus in the Shaanxi Province and provide the basis for the future development of control measures, this article aims to report the epidemiological outcomes of the 195 confirmed cases infected with SARS-CoV-2 and to compare the clinical features between patients with or without a history of exposure in Wuhan. Patients confirmed with novel coronavirus pneumonia in Shaanxi Province mainly have a history of Wuhan contact. There are characteristics of family aggregation and concealment. http://bit.ly/2x7xs1V
Walking on Eggshells: Parents’ First Year After Their Adolescent Completes Their Cancer Treatment

Background: Despite an awareness that parents experience distress and heightened uncertainty at the end of their adolescent’s treatment for cancer, little is known about the specific challenges and concerns parents hold for their adolescent survivors or how they manage these challenges. This study described challenges parents experience in the first year after their adolescent’s cancer treatment and what parents did to manage those challenges. Method: Single occasion semistructured interviews were conducted with parents and were transcribed verbatim. Data were coded using inductive content analysis methods adapted from grounded theory. Results: Participants were 30 parents of adolescent survivors (13-18 years) who were in the first year following treatment completion. The core construct, “Walking on Eggshells,” explained the processes and experiences parents faced once treatment was complete. Two additional domains captured how parents managed posttreatment challenges (“Doing What We Can”) and the ways parents helped their adolescents adjust (“Balancing”). Conclusion: Study results suggest that services and materials are needed to help parents know common struggles that arise after treatment and ways to mitigate the severity of distress parents experience.
The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients.

OBJECTIVES To examine the effect of lymphadenectomy on survival in patients with squamous cell vulvar carcinoma. MATERIAL AND METHODS Patients with squamous cell vulvar cancer who underwent surgery were retrospectively analyzed. All procedures were performed according to current recommendations/standard of treatment. The clinical and pathological features were examined. Sixty-eight patients were studied. The mean age was 64.7 ± 10.9 years. Twenty-three (33.8%) patients had nodal metastasis. Most patients (60.3%) were in stage IB. Adjuvant radiotherapy and chemo-radiotherapy were administered to 33.8% and 25% of the patients, respectively. The median follow-up time was 28.5 (4-183) months. Recurrence occurred in 18 (26.5%) cases. RESULTS There was no significant difference between node-positive and node-negative patients in terms of age, number of dissected lymph nodes and recurrence. Tumor diameter was significantly higher in the metastatic group. Age and surgical margin positivity were independent prognostic factors for overall survival (OS). Surgical margin positivity and lymph node metastasis had no effect on disease-free survival (DFS). CONCLUSIONS Our results showed that age and surgical margin positivity were independent prognostic factors for OS. Although surgical margin positivity increased the risk of recurrence in univariate analysis, it was not a significant factor affecting DFS. OS was significantly lower in patients with lymph node metastasis.
Prognostic Value of Teratoma in Primary Tumor and Postchemotherapy Retroperitoneal Lymph Node Dissection Specimens in Patients With Metastatic Germ Cell Tumor.

PURPOSE Presence of teratoma in patients with metastatic testicular germ cell tumor (GCT) is of unknown prognostic significance. We report survival outcomes of patients with or without teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen and assess impact on prognosis. PATIENTS AND METHODS Patients with metastatic nonseminomatous GCT (NSGCT) who were evaluated at Indiana University between 1990 and 2016 and had primary testicular tumor specimen from orchiectomy (ORCH) were included. All patients were treated with cisplatin-based combination chemotherapy. The cohort was divided into 2 groups according to presence or absence of teratoma in ORCH specimen. Survival data were correlated with histopathologic findings. Differences in progression-free (PFS) and overall survival (OS) were evaluated using log-rank tests and Cox proportional hazards models to adjust for known adverse prognostic factors. RESULTS We identified 1,224 consecutive patients evaluated at Indiana University between 1990 and 2016 who met inclusion criteria. Median age was 27 years (range, 13-71 years); 689 patients had teratoma in ORCH specimen, and 535 did not. With median follow-up of 2.3 years, 5-year PFS was 61.9% (95% CI, 57.1% to 66.2%) for those with teratoma versus 63.1% (95% CI, 58.0% to 67.8%) for those without (P = .66); 5-year OS was 82.2% (95% CI, 77.9% to 85.8%) versus 81.4% (95% CI, 76.5% to 85.3%; P = .91), respectively. A total of 473 patients underwent PC-RPLND; 5-year PFS for patients with pure teratoma in PC-RPLND specimen versus necrosis only was 65.9% versus 79.1% (P = .06), and 5-year OS was 90.3% versus 93.4% (P = .21), respectively. CONCLUSION Presence of teratoma in ORCH and PC-RPLND specimens was not a prognostic factor in this large retrospective study of patients with NSGCT.
Incidence of anorexia nervosa and its associated symptoms among females in diverse profession groups in district Kohat and Karak

Anorexia nervosa is also sometime called Anorexia. It is psychological disorder in which is prevalent among females. 618 adult respondents of various professions were included in this study out of which 77/618 were Teachers, 138/618 were house wives, 97/618 were unmarried house hold females, 109/618 were College and university students, 80/618 were social workers, 35/618 were paramedic staff, 9/618 were female security guards, 8/618 were lady constables, 32/618 were maids, 15/618 were female tailors while 18 were doctors. Data was recorded on a questionnaire. Almost all females were either completely or partially suffering from anorexia nervosa as they had fear of becoming over weight. About Excessive exercise (64/618) and induced vomiting (67/618) was found most prevalent symptoms present among of study population. 41/618 were involved in skipping meals, 30/618 were using laxatives, 36/618 were hypothermic, 29/618 had brittle nails due to malnutrition, 41/618 had thin appearance still they were involved in reducing weight, 29/618 had amenorrhea, 40/618 had depression, 3/618 3 had fatigue, 39 had mood swing problem, 43/618 had dry skin, 26/618 had fear of gaining weight, 37/618 had constipation problem, 26/618 had hypotension, 8/618 had hypertension, 29/618 had halitosis
Development of a methodology to make individual estimates of the precision of liquid chromatography-tandem mass spectrometry drug assay results for use in population pharmacokinetic modeling and the optimization of dosage regimens

Background The clinical value of therapeutic drug monitoring can be increased most significantly by integrating assay results into clinical pharmacokinetic models for optimal dosing. The correct weighting in the modeling process is 1/variance, therefore, knowledge of the standard deviations (SD) of each measured concentration is important. Because bioanalytical methods are heteroscedastic, the concentration-SD relationship must be modeled using assay error equations (AEE). We describe a methodology of establishing AEE’s for liquid chromatography-tandem mass spectrometry (LC-MS/MS) drug assays using carbamazepine, fluconazole, lamotrigine and levetiracetam as model analytes. Methods Following method validation, three independent experiments were conducted to develop AEE’s using various least squares linear or nonlinear, and median-based linear regression techniques. SD’s were determined from zero concentration to the high end of the assayed range. In each experiment, precision profiles of 6 (“small” sample sets) or 20 (“large” sample sets) out of 24 independent, spiked specimens were evaluated. Combinatorial calculations were performed to attain the most suitable regression approach. The final AEE’s were developed by combining the SD’s of the assay results, established in 24 specimens/spiking level and using all spiking levels, into a single precision profile. The effects of gross hyperbilirubinemia, hemolysis and lipemia as laboratory interferences were investigated. Results Precision profiles were best characterized by linear regression when 20 spiking levels, each having 24 specimens and obtained by performing 3 independent experiments, were combined. Theil’s regression with the Siegel estimator was the most consistent and robust in providing acceptable agreement between measured and predicted SD’s, including SD’s below the lower limit of quantification. Conclusions In the framework of precision pharmacotherapy, establishing the AEE of assayed drugs is the responsibility of the therapeutic drug monitoring service. This permits optimal dosages by providing the correct weighting factor of assay results in the development of population and individual pharmacokinetic models.
The Longitudinal Parallel Process Analysis of Biomarkers of Oxidative Stress, Symptom Clusters, and Cognitive Function in Children With Leukemia

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar punctures. GSH biomarkers, symptoms, and cognitive function of 132 children aged 3 to 18 years were evaluated at four time points during the first year of leukemia treatment. Participants, 7 years and older, completed self-report measures, and parents reported for younger children. Cognitive function measurements for all participants were completed by parents. A longitudinal parallel-process model was used to explore the influence of the initial measurement and the subsequent change over four time points of the GSH biomarkers on the CCSC-L and cognition. Results: GSH biomarkers increased over the four time points indicating decreasing oxidative stress. When GSH biomarkers were higher (less oxidative stress) at the initial measurement, the CCSC-L severity was lower, cognition was better, and cognition improved over the four measurements. Screening children for high levels of oxidative stress would be a foundation for future intervention studies to address symptom distress and cognitive impairments.
Gestational age at antenatal booking In lagos, south-west nigeria

Early booking, prior to fourteen weeks gestation is usually recommended to achieve improved outcome of pregnancy for the mother and the fetus.A survey of information among patients attending post-natal clinic at Lagos State University Teaching Hospital, Ikeja, Lagos Nigeria was carried out using a structured questionnaire. The mean gestational age at booking was 23.5(+6.9) weeks. Only 23(6%) booked before 14 weeks gestation.The reasons given for late booking were mandatory blood donation of one pint of blood to the hospital’s blood bank by the husband or the relative (44%), convenience (25%), the logistics involved in registration (24%), affordability (3%) while relocation and assurance of a live fetus (quickening) contributed 2% each. The need to educate women in the reproductive age group on the importance of early booking is recommended. It is also recommended that the logistics involved in registration and blood donation should be reviewed.
Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice

Amyloid plaques in Alzheimer’s disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aβ) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the Aβ burden prior to brain, highlighting gut–brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular Aβ deposition in the IEB occur before cerebral Aβ aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral Aβ pathology. Lastly, we report Aβ deposition in the intestinal autopsy from AD patients with confirmed cerebral Aβ pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota.
Thermosensitive Hydrogel for Encapsulation and Controlled Release of Biocontrol Agents to Prevent Peanut Aflatoxin Contamination

Starch, alginate, and poly(N-isopropylacrylamide) (PNIPAAm) were combined to prepare a semi-interpenetrating network (IPN) hydrogel with temperature sensitivity. Calcium chloride was used as cross-linking agent, the non-toxigenic Aspergillus flavus spores were successfully encapsulated as biocontrol agents by the method of ionic gelation. Characterization of the hydrogel was performed by Fourier-transform infrared spectroscopy (FTIR), scanning electron micrograph (SEM), and thermogravimetry analysis (TGA). Formulation characteristics, such as entrapment efficiency, beads size, swelling behavior, and rheological properties were evaluated. The optical and rheological measurements indicated that the lower critical solution temperature (LCST) of the samples was about 29–30 °C. TGA results demonstrated that the addition of kaolin could improve the thermal stability of the semi-IPN hydrogel. Morphological analysis showed a porous honeycomb structure on the surface of the beads. According to the release properties of the beads, the semi-IPN hydrogel beads containing kaolin not only have the effect of slow release before peanut flowering, but they also can rapidly release biocontrol agents after flowering begins. The early flowering stage of the peanut is the critical moment to apply biocontrol agents. Temperature-sensitive hydrogel beads containing kaolin could be considered as carriers of biocontrol agents for the control of aflatoxin in peanuts.
Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross‐sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.