Miracle-dz/UniFAR-FTUs huggingface dataset:
PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect.

Oxaliplatin (OXA) was coupled to PEGylated polyamidoamine dendrimers of fourth generation (G4-PEG@OXA) in the comparison to PEGylated ones of odd generation (G3.5-PEG@OXA). Proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy were used to confirm the successful incorporation of OXA as well as the synthesis of carrier systems. Both two types of carrier systems exhibited in sphere nanoparticle shape with size of less than 100 nm that was in the range being able to cause toxicity on cancer cells. The average drug loading efficiency (DLE) of G4-PEG@OXA was obtained at 84.63% that was higher than DLE of G3.5-PEG of 75.69%. The release kinetic of G4-PEG@OXA and G3.5-PEG@OXA did not show any burst release phenomenon while free OXA was released over 40% at the first hour. The sustainable release of OXA was achieved when it was encapsulated in these carriers, but the G4 generation liberated OXA (3.4%-6.4%) slower than G3.5 one (11.9%-22.8%). The in vitro cytotoxicities of G4-PEG@OXA were evaluated in HeLa cell lines using resazurin assay and live/dead staining test. Although the free OXA showed a rather moderate killing ability, the G4-PEG@OXA still displayed the low viability of HeLa that was better to the result of G3.5-PEG@OXA due to released OXA amount. The benefit of this system was to overcome the burst release phenomenon to minimize OXA toxicity without compromising its efficiency.
Finasteride and androgenic alopecia; from therapeutic options to medical implications

Abstract Androgenic alopecia (AGA) is an esthetic condition with varying psycho-social implications, easily accepted by some patients and tolerated only with difficulty by others. Modern therapeutic options such as 5α-reductase inhibitors have significant outcomes, but also exert significant side effects in a subset of patients. The literature describes three distinct situations regarding finasteride administration, a compound largely used for AGA. Some studies show finasteride to be very safe with minimal or no side effects. Other studies take a more cautious approach, recognizing such side effects but, at the same time, considering the putative relationship between finasteride and adverse effects to be disputable, given that placebo administration in AGA is associated with relatively similar or even more severe side effects. Finally, some authors/studies are concerned that, when compared to placebo, finasteride administration may result in side effects with greater frequency and severity, and sometimes that persist even after treatment cessation in the form of post-finasteride syndrome. Several factors presented in this paper appear to explain finasteride inconsistency regarding its therapeutic and side effects. Such factors should be further investigated and used to categorize subjects into distinct subgroups, either predisposed to adverse reactions or more tolerant of the finasteride administration.
Psychological and psychosocial interventions offered to forensic mental health inpatients: a systematic review

Objective To examine the evidence for the use of psychological and psychosocial interventions offered to forensic mental health inpatients. Design CINAHL, MEDLINE, PsycINFO, ScienceDirect and Web of Science databases were searched for research published in English between 1 January 1990 and 31 May 2018. Outcome measures Disturbance, mental well-being, quality of life, recovery, violence/risk, satisfaction, seclusion, symptoms, therapeutic relationship and ward environment. There were no limits on the length of follow-up. Eligibility criteria We included randomised controlled trial (RCT) studies of any psychological or psychosocial intervention in an inpatient forensic setting. Pilot or feasibility studies were included if an RCT design was used. We restricted our search criteria to inpatients in low, medium and high secure units aged over 18. We focused on interventions considered applicable to most patients residing in forensic mental health settings. Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias. Results 17 232 citations were identified with 195 full manuscripts examined in detail. Nine papers were included in the review. The heterogeneity of the identified studies meant that meta-analysis was inappropriate. The results were presented in table form together with a narrative synthesis. Only 7 out of 91 comparisons revealed statistically significant results with no consistent significant findings. The most frequently reported outcomes were violence/risk and symptoms. 61% of the violence/risk comparisons and 79% of the symptom comparisons reported improvements in the intervention groups compared with the control groups. Conclusions Current practice is based on limited evidence with no consistent significant findings. This review suggests psychoeducational and psychosocial interventions did not reduce violence/risk, but there is tentative support they may improve symptoms. More RCTs are required with: larger sample sizes, representative populations, standardised outcomes and control group interventions similar in treatment intensity to the intervention. PROSPERO registration number CRD42017067099.
Hypertension in CKD: Core Curriculum 2019.

Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that sustained hypertension can lead to worsening kidney function and progressive decline in kidney function can conversely lead to worsening blood pressure (BP) control. The pathophysiology of hypertension in CKD is complex and is a sequela of multiple factors, including reduced nephron mass, increased sodium retention and extracellular volume expansion, sympathetic nervous system overactivity, activation of hormones including the renin-angiotensin-aldosterone system, and endothelial dysfunction. Currently, the treatment target for patients with CKD is a clinic systolic BP < 130mm Hg. The main approaches to the management of hypertension in CKD include dietary salt restriction, initiation of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic therapy. Uncontrolled hypertension can lead to significant cardiovascular morbidity and mortality and accelerate progression to end-stage kidney disease. Although intensive BP control has not been shown in clinical trials to slow the progression of CKD, intensive BP control reduces the risk for adverse cardiovascular outcomes and mortality in the CKD population.
Child Developmental Disabilities, Caregivers’ Role in Kenya and Its Implications on Global Migration

Background: This paper is a summary of the findings from an ethnographic study on child developmental disabilities conducted partly in Nairobi and Kiambu Counties in Kenya. Methods: Quantitative and qualitative data collection methods were applied for the period between mid August and mid November 2018. The study was conducted through the Kenya Institute of Special Education (KISE) situated in Nairobi County. Results: There are parents who are willing to migrate in search of better education and healthcare options for their children who have developmental disabilities (DDs). However, there are also government reforms taking place in the field of disability that may help to support the caregiving role for children with special needs. The challenges, bargaining position and power play between parents or guardians and other actors implicated in the debates on inclusion and integration of persons with developmental disabilities in Kenya has been brought to the forefront. Conclusions: In Kenya, more needs to be done to change the attitude towards disability from the medical and moral (religious/cultural) models to an approach leaning towards the social model, so that developmental disabilities are not viewed negatively.
Anthropogenic basin closure and groundwater salinization (ABCSAL)

Abstract Global food systems rely on irrigated agriculture, and most of these systems in turn depend on fresh sources of groundwater. In this study, we demonstrate that groundwater development, even without overdraft, can transform a fresh, open basin into an evaporation dominated, closed-basin system, such that most of the groundwater, rather than exiting via stream baseflow and lateral subsurface flow, exits predominantly by evapotranspiration from irrigated lands. In these newly closed hydrologic basins, just as in other closed basins, groundwater salinization is inevitable because dissolved solids cannot escape, and the basin is effectively converted into a salt sink. We first provide a conceptual model of this process, called “Anthropogenic Basin Closure and groundwater SALinization” (ABCSAL). We examine the temporal dynamics of ABCSAL using the Tulare Lake Basin, California, as a case study for a large irrigated agricultural region with Mediterranean climate, overlying an unconsolidated sedimentary aquifer system. Even with modern water management practices that arrest historic overdraft, results indicate that shallow aquifers (36 m deep) exceed maximum contaminant levels for total dissolved solids on decadal timescales. Intermediate (132 m) and deep aquifers (187 m), essential for drinking water and irrigated crops, are impacted within two to three centuries. Hence, ABCSAL resulting from groundwater development constitutes a largely unrecognized constraint on groundwater sustainable yield on similar timescales to aquifer depletion in the Tulare Lake Basin, and poses a serious challenge to groundwater quality sustainability, even when water levels are stable. Results suggest that agriculturally intensive groundwater basins worldwide may be susceptible to ABCSAL.
Intermittent Fasting in Cardiovascular Disorders—An Overview

Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation).
Influence of Environmental Parameters on Microbiologically Influenced Corrosion Subject to Different Bacteria Strains

Microbiologically influenced corrosion (MIC) is capable on weakening the metal’s strength, eventually leads to pipeline leakage, environmental hazard and financial loss. Sulfate reducing bacteria (SRB) is the principal causative organism responsible for external corrosion on steel structures. To date, considerable works have been conducted in Malaysia on the mechanisms of SRB upon MIC on the marine environment instead of underground. Moreover, commercial bacteria strain represents local strain in terms of performance and behavior upon corrosion of steel structure is yet to be proven. Thus, this paper aims to investigate the influence of environmental parameters towards MIC in corroding pipeline. Two types of SRB strain were used designated as SRB ATCC 7757 (commercial) and SRB Sg. Ular (local strain) isolated from Malaysian soil. The behavior of both strains was critically compared by calculating the rate of corrosion upon carbon steel coupons in stipulated environmental parameters. Four influential parameters i.e. pH, temperature, salinity concentration and iron concentration were considered. Collected data presented and analyzed using graphical and statistical analysis, respectively. The results showed the difference of corrosivity between two SRB strains in terms of corrosion behavior upon the X-70 steel coupon. SRB Sg. Ular able to cause severe effects upon steel structure as compared to SRB ATCC 7757 due to its aggressiveness shown by the recorded metal loss data. Thus, future works related to MIC for local environment in particular, should not compromise with the type of SRB strains considered due to differences of performance of the microorganisms onto tested environment and materials.
A meta-analysis of the relationship between moral disengagement and bullying roles in youth.

Over the last several years, researchers have become increasingly interested in the influence of moral factors on bullying behaviors. This is the first meta-analytic review to exclusively examine the relationship between moral disengagement (MD) and the key bullying roles of bully, victim, defender, and bystander. Forty-seven independent samples examining a total of 43,809 children/adolescents (aged 7-19) were included in this meta-analysis. Results indicated a positive relationship between MD and bullying (r = 0.31; 95% CI [0.27, 0.34]), MD and victimization (r = 0.08; 95% CI [0.05, 0.12]), and a negative relationship between MD and defending (r = -0.11; 95% CI [-0.17, -0.04]). No significant relationship was found for MD and bystanding behavior. Moderators of bullying type (traditional vs. cyberbullying), reporting type (self vs. peer report), age, and gender were included in the analyses. The results are discussed in the context of relevant literature with particular emphasis on the importance of distinguishing between guilty and unconcerned bystanders, and the significant overlap between bullying and victimization in the cyber context.
Pathophysiology of refractory overactive bladder

Overactive bladder (OAB) is a common condition. The International Continence Society defines OAB as a symptom complex characterized by urgency with or without urge incontinence, usually with frequency and nocturia. The first‐line treatment for OAB includes behavioral therapy, such as caffeine reduction, fluid intake modification, weight reduction, bladder training, and pelvic floor muscle training, as well as treatment with antimuscarinic or β3‐adrenoceptor agonist medications. However, less than half of all cases achieve satisfactory outcomes following first‐line treatment. Second‐line therapy considered if satisfactory responses are not achieved after 8 to 12 weeks treatment with first‐line therapy include intradetrusor botulinum toxin injection, neuromodulation, and surgical treatment. Patients with refractory OAB may have more severe symptoms or underlying pathophysiologies that were not resolved by the initial medication. The pathophysiologies of refractory OAB include occult neurogenic bladder, undetected bladder outlet obstruction, urethral‐related OAB, urothelial dysfunction with aging, chronic bladder ischemia, chronic bladder inflammation, central sensitization, and autonomic dysfunction. This article discusses the possible pathophysiologies of refractory OAB.
End-of-life cost and its determinants for cancer patients in urban China: a population-based retrospective study

Objective This study aimed to define the end-of-life (EOL) healthcare utilisation and its cost and determinants for cancer patients and to proactively inform related strategies in mainland China. Design A population-based retrospective study. Setting and participants Data from 894 cancer patients were collected in urban Yichang, China from 01 July 2015 to 30 June 2017. Outcome measures Emergency department (ED) visits, outpatient and inpatient hospitalisation services, intensive care unit (ICU) admission and total costs were used as the main outcomes. Results In this study, 66.8% of the 894 patients were male, and the average age was 60.4 years. Among these patients, 37.6% died at home, and patients had an average of 4.86 outpatient services, 2.23 inpatient hospitalisation services and 1.44 ED visits. Additionally, 5.9% of these patients visited the ICU at least once. During the EOL periods, the costs in the last 6 months, 3 months, 1 month and 1 week were US$18 234, US$13 043, US$6349 and US$2085, respectively. The cost increased dramatically as death approached. The estimation results of generalised linear regression models showed that aggressive care substantially affected expenditure. Patients with Urban Employee Basic Medical Insurance spent more than those with Urban Resident-based Basic Medical Insurance or the New Rural Cooperative Medical Scheme. The place of death and the survival time are also risk factors for increased EOL cost. Conclusion The findings suggested that the EOL cost for cancer patients is associated with aggressive care, insurance type and survival time. Timing palliative care is urgently needed to address ineffective and irrational healthcare utilisation and to reduce costs. Ethics and dissemination This study was approved by the Ethics Committee of the Tongji Medical College, Huazhong University of Science and Technology (IORG No.: IORG0003571). All the data used in this study were de-identified.
Gesturing tool use and tool transport actions modulates inferior parietal functional connectivity with the dorsal and ventral object processing pathways

Interacting with manipulable objects (tools) requires the integration of diverse computations supported by anatomically remote regions. Previous functional neuroimaging research has demonstrated the left supramarginal (SMG) exhibits functional connectivity to both ventral and dorsal pathways, supporting the integration of ventrally‐mediated tool properties and conceptual knowledge with dorsally‐computed volumetric and structural representations of tools. This architecture affords us the opportunity to test whether interactions between the left SMG, ventral visual pathway, and dorsal visual pathway are differentially modulated when participants plan and generate tool‐directed gestures emphasizing functional manipulation (tool use gesturing) or structure‐based grasping (tool transport gesturing). We found that functional connectivity between the left SMG, ventral temporal cortex (bilateral fusiform gyri), and dorsal visual pathway (left superior parietal lobule/posterior intraparietal sulcus) was maximal for tool transport planning and gesturing, whereas functional connectivity between the left SMG, left ventral anterior temporal lobe, and left frontal operculum was maximal for tool use planning and gesturing. These results demonstrate that functional connectivity to the left SMG is differentially modulated by tool use and tool transport gesturing, suggesting that distinct tool features computed by the two object processing pathways are integrated in the parietal lobe in the service of tool‐directed action.
Time-Resolved Macromolecular Crystallography at Pulsed X-ray Sources

The focus of structural biology is shifting from the determination of static structures to the investigation of dynamical aspects of macromolecular function. With time-resolved macromolecular crystallography (TRX), intermediates that form and decay during the macromolecular reaction can be investigated, as well as their reaction dynamics. Time-resolved crystallographic methods were initially developed at synchrotrons. However, about a decade ago, extremely brilliant, femtosecond-pulsed X-ray sources, the free electron lasers for hard X-rays, became available to a wider community. TRX is now possible with femtosecond temporal resolution. This review provides an overview of methodological aspects of TRX, and at the same time, aims to outline the frontiers of this method at modern pulsed X-ray sources.
Kinetics of Physiological and Behavioural Responses in Endotoxemic Pigs with or without Dexamethasone Treatment

Although dexamethasone (DEX) is a widely used immunoregulatory agent, knowledge about its pharmacological properties in farm animals, especially pigs, is insufficient. Previous studies suggest that compared to other species, pigs are less sensitive to the immunosuppression conferred by DEX and more sensitive to the threat of bacterial endotoxins. However, there is a paucity of studies examining DEX immunomodulation in endotoxemia in this species. In this study, a porcine endotoxemia model was established by lipopolysaccharide (LPS) and the effect of DEX-pretreatment on the magnitude and kinetics of neuroendocrine, metabolic, hematologic, inflammatory, and behavioural responses were examined. DEX decreased cortisol, adrenocorticotropic hormone (ACTH), red blood cell, hemoglobin, hematocrit, and lymphocyte whereas glucose concentration was increased under both normal and endotoxemic conditions. By contrast, DEX decreased triglyceride, lactate, and IL-6 concentrations and increased platelet count only under an endotoxemic condition. DEX also reduced the frequency of sickness behaviour following LPS challenge. PCA showed that glucose and triglyceride metabolism together with red blood cell count mainly contributed to the separation of clusters during DEX treatment. Our study demonstrates that DEX protects pigs from inflammation and morbidity in endotoxemia, in spite of their less sensitivity to DEX. Moreover, its considerable role in the regulation of the metabolic and hematologic responses in endotoxemic pigs is revealed for the first time.
Side of Hamstring Harvest Does Not Affect Performance, Return-to-Sport Rate, or Future Hamstring Injuries After Ulnar Collateral Ligament Reconstruction Among Professional Baseball Pitchers

Background: Ulnar collateral ligament reconstruction (UCLR) is a successful procedure among professional baseball pitchers. It is unclear if hamstring tendon harvest side for UCLR affects the outcome or alters the risk for subsequent hamstring injury. Hypothesis: Players with prior UCLR with ipsilateral (drive leg) hamstring autograft will have the same return-to-sport (RTS) rate and performance upon RTS but a higher number of subsequent lower extremity injuries than those with contralateral (landing leg) hamstring autograft. Study Design: Cohort study; Level of evidence, 3. Methods: All players between 2010 and 2015 who underwent UCLR with hamstring autograft were included. Surgical details of their procedures were recorded from operative reports. Outcomes for UCLR with hamstring autograft harvested from the drive leg were compared with UCLR with the graft harvested from the landing leg. Results: Overall, 191 players underwent UCLR with hamstring autograft (drive leg, n = 58, 30%; landing leg, n = 133, 70%). The docking technique was more common in the drive leg group, while the figure-of-8 technique was more common in the landing leg group (P > .001). More patients in the landing leg group underwent concomitant treatment of the ulnar nerve than the drive leg group (P < .001). No difference existed in RTS rates or timing of RTS between groups. No differences in subsequent ipsilateral or contralateral hamstring injuries occurred between players who underwent UCLR with hamstring autograft from the drive leg or the landing leg (P≥ .999 and P = .460, respectively). No difference in overall upper or lower extremity injury rates existed between groups (all P > .05), and no difference in performance metrics existed between groups upon RTS. Conclusion: No difference in RTS rate, performance upon RTS, or subsequent injury rates (hamstring, lower extremity, or upper extremity) existed between players who underwent UCLR with hamstring autograft whether the graft came from the drive or the landing leg.