Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormonal changes in consecutive clomiphene citrate stimulation cycles and their effect on pregnancy rates

Objective: To determine the relationship between the cumulative effect of sequential clomiphene citrate (CC) treatments in unexplained infertile women with intercycle and intracycle serum hormone changes. Materials and Methods: Patients who received CC 50 mg in the first cycle (group I, n=34) as ovulation induction and those who received CC 50 mg in the second consecutive cycle (group II, n=18) were compared. Basal (cycle days 2-5) and trigger day (the day that recombinant human chorionic gonadotropin is given) levels of gonadotropin and steroid hormones were measured. Results: The 17OHP increase on trigger day was found to be statistically significantly higher in group II compared to the basal day (p=0.083). The testosterone (T) response on the trigger day of the patients in group II was found to be statistically significantly higher than that in group I (p=0.023). The number of selected follicles was negatively correlated with a follicle-stimulating hormone decrease and positively correlated with an estradiol increase. Endometrial thickness was positively correlated with a luteinizing hormone increase, and cycle cancelation was positively correlated with decreased estradiol. Conclusion: Based on this study, it was concluded that the reason for the increased efficiency rate in successive cycles of CC may be the cumulative increase in T and 17OHP levels. However, this result was found not to affect the clinical pregnancy rate.
Highly Effective Multifunctional Solar Evaporator with Scaffolding Structured Carbonized Wood and Biohydrogel.

A solar evaporator that utilizes solar radiation energy can be a renewable approach to deal with energy crisis and fresh water shortage. In this study, a solar evaporator was prepared by assembling composite carbonized wood of Melaleuca Leucadendron L. and biobased hydrogel. The multilayer MXene (Ti3C2Tx) was embedded in the scaffolding structure of the wood to form composite carbonized wood, where the loose and ordered scaffolding structure of the carbonized wood significantly improves the efficiency of water transportation with increased capillary force. The MXene adsorbed in the carbonized wood has high binding energy with water molecules, leading to reduction of vaporization enthalpy and contact angle. Moreover, the addition of MXene can improve the light absorbance, especially for the infrared and ultraviolet light bands. The hydrogel was fabricated by crosslinking konjac glucomannan and sodium alginate polysaccharides with Ca2+, and it has a lower thermal conductivity than water and improves the evaporation efficiency by regulating the temperature distribution and concentrating the heat on the surface of the evaporator. This solar evaporator has an evaporation rate of 3.71 kg·m-2·h-1 and an evaporation efficiency of 129.64% under 2 sun illumination and is available to generate an open-circuit voltage of 1.8 mV after a 20 min hydrovoltaic, demonstrating a high performance and versatility. Also, experiments and numerical simulation were carried out to understand the mechanism and design principles of this solar evaporators.
Are sunspot penumbrae deep or shallow

From the strength and inclination of the magnetic field measured across large symmetric sunspots we estimate the fraction of the total magnetic flux of the sunspot passing through the solar surface in the penumbra. It is found that on average approximately 1/2-2/3 of the total magnetic flux of the spot emerges in its penumbra. Sunspot penumbrae are therefore deep, i.e. the τ=1 level does not correspond to the lower magnetic boundary of the spot in its penumbra (except perhaps near its outer edge). Furthermore, the analysed data do not support the passage of any significant amount of magnetic flux through the solar surface (in either direction) at or beyond the edge of the sunspot
Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT and is associated with pulmonary hypertension.

Mechanical forces are translated into biochemical stimuli by mechanotransduction channels, such as the mechanically-activated cation channel Piezo2. Lung Piezo2 expression has recently been shown to be restricted to endothelial cells. Hence, we aimed to investigate the role of Piezo2 in regulation of pulmonary vascular function and structure as well as its contribution to development of pulmonary arterial hypertension (PAH). The expression of Piezo2 was significantly reduced in pulmonary microvascular endothelial cells (MVECs) from PAH patients, in lung tissue from mice with a Bmpr2+/R899X knock-in mutation commonly found in pulmonary hypertension patients, and in lung tissue of MCT and SuHx PAH rat models as well as from a swine model with pulmonary vein banding. In MVECs, Piezo2 expression was reduced in response to abnormal shear stress, hypoxia and TGFβ stimulation. Functional studies in MVECs exposed to shear stress illustrated that siRNA-mediated Piezo2 knockdown impaired endothelial alignment, calcium influx, phosphorylation of AKT and nitric oxide production. In addition, siPiezo2 reduced the expression of the endothelial marker PECAM-1 and increased expression of vascular smooth muscle markers ACTA2, SM22a and Calponin. Thus, Piezo2 acts as a mechanotransduction channel in pulmonary MVECs, stimulating shear-induced production of nitric oxide and is essentially involved in preventing endothelial to mesenchymal transition. Its blunted expression in pulmonary hypertension could impair the vasodilator capacity and stimulate vascular remodelling, indicating that Piezo2 might be an interesting therapeutic target to attenuate progression of the disease.
DARWIN mission proposal to ESA

The discovery of extra-solar planets is one of the greatest achievements of modern astronomy. There are now more than 200 such objects known, and the recent detection of planets with masses approximately 5 times that of Earth demonstrates that extra-solar planets of low mass exist. In addition to providing a wealth of scientific information on the formation and structure of planetary systems, these discoveries capture the interest of both scientists and the wider public with the profound prospect of the search for life in the Universe. We propose an L-type mission, called Darwin, whose primary goal is the study of terrestrial extrasolar planets and the search for life on them. By its very nature, Darwin advances the first Grand Theme of ESA Cosmic Vision. Accomplishing the mission objectives will require collaborative science across disciplines ranging from planet formation and atmospheres to chemistry and biology, and these disciplines will reap profound rewards from their contributions to the Darwin mission.
Ca2+‐independent transmission at the central synapse formed between dorsal root ganglion and dorsal horn neurons

A central principle of synaptic transmission is that action potential‐induced presynaptic neurotransmitter release occurs exclusively via Ca2+‐dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+‐independent but voltage‐dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here, we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons in vitro, (i) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (ii) CiVDS‐mediated EPSCs are independent of extracellular and intracellular Ca2+; (iii) CiVDS is faster than CDS in vesicle recycling with much less short‐term depression; (iv) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity‐induced EPSCs is mediated by CiVDS in a central synapse.
Photodynamic Therapy for Bladder Cancers, A Focused Review †

Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non‐muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non‐muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX‐PDT, we have been working on combining it with singlet oxygen‐activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX‐PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off‐target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.
Fijian medicinal plants and their role in the prevention of Type 2 diabetes mellitus

Abstract Medicinal plants (MPs) are natural sources of active compounds with potential therapeutic benefits in alleviating various illnesses for decades. Fijian people also are using these MPs for the management/prevention of Type 2 diabetes mellitus (T2DM) and associated complications. However, till date, none of these Fijian MP’s antidiabetic potential have been explored or evaluated. Here, we investigated the antidiabetic potential of Fijian MPs scientifically. Phytochemicals such as polyphenols were detected to inhibit the activity of α-amylase and α-glucosidase, the two key carbohydrate enzymes linked to T2DM. Therefore, in the present study, the total phenolic content (TPC), α-amylase and α-glucosidase inhibitory activity of five Fijian MPs: Vobo (Mussaenda raiateensis, MR), Vula walu (Blechnum orientale, BO), Gasau (Miscanthus floridulus, MF), Molikaro (Citrus limon, CL) and Beki ni sina (Dicranopteris caudate, DC) collected from mainland region of Vitilevu, Fiji Islands, were evaluated in vitro. The hydromethanolic (ME) and dichloromethane (DM) extracts of these selected MPs were investigated. The ME extracts of BO (0.102 ± 0.009 mM CE) and DC (0.098 ± 0.09 mM Catechin Equivalence [CE]) showed a higher TPC compared with the control [vanillic acid (0.052 ± 0.003 mM CE, *P value < 0.05)]. However, the TPC of MF, MR and CL were found in the range of 0.020 ± 0.009 to 0.009 ± 0.01 mM CE. The ME extracts of MF and MR inhibited α-glucosidase significantly in comparison with acarbose as evidenced from the IC50 values (IC50 of MF = 1.58 ± 0.03 ng/µl; IC50 of MR = 1.87 ± 0.43 ng/µl and IC50 of acarbose = 3.34 ± 0.15 ng/µl). Moreover, DM extracts of MR (IC50 = 1.31 ± 0.29 ng/µl) also showed significantly higher α-glucosidase inhibitory activity. In contrary, MR (IC50 = 16.18 ± 0.16 ng/µl) and CL (IC50 = 9.21 ± 0.51 ng/µl) also showed significant α-amylase inhibitory activity in ME and DM extracts, respectively. These, results suggest that Fijian MPs could be a potential source of natural inhibitors of enzymes involved in carbohydrate digestion and thus may possibly be used in managing T2DM.
Approaches to Estimating Clearance Rates for Human Papillomavirus Groupings: A Systematic Review and Real Data Examples

Introduction: Approaches to estimating clearance rates, an important metric of human papillomavirus (HPV) clearance, for HPV groupings differ between studies. We aimed to identify the approaches used in the literature for estimating grouped HPV clearance rates. We investigated whether these approaches resulted in different estimations, using data from existing studies. Methods: In this systematic review, we included articles that reported clearance rates of HPV groupings. We identified approaches to data in the HAVANA cohort, comprising adolescent girls, and the H2M cohort, comprising men who have sex with men. We estimated clearance rates for six HPV groupings (bivalent-, quadrivalent- and nonavalent vaccine-related, and low-risk, high-risk, and any HPV). Results: From 26 articles, we identified 54 theoretically possible approaches to estimating clearance rates. These approaches varied regarding definitions of clearance events and person–time, and prevalence or incidence of infections included in the analysis. Applying the nine most-used approaches to the HAVANA (n = 1,394) and H2M (n = 745) cohorts demonstrated strong variation in clearance rate estimates depending on the approach used. For example, for grouped high-risk HPV in the H2M cohort, clearance rates ranged from 52.4 to 120.0 clearances/1000 person–months. Clearance rates also varied in the HAVANA cohort, but differences were less pronounced, ranging from 24.1 to 57.7 clearances/1000 person–months. Conclusions: Varied approaches from the literature for estimating clearance rates of HPV groupings yielded different clearance rate estimates in our data examples. Estimates also varied between study populations. We advise clear reporting of methodology and urge caution in comparing clearance rates between studies.
Perioperative Neurocognitive Disorders in Adults Requiring Cardiac Surgery: Screening, Prevention, and Management

Neurocognitive changes are the most common complication after cardiac surgery, ranging from acute postoperative delirium to prolonged postoperative neurocognitive disorder. Changes in cognition are distressing to patients and families and associated with worse outcomes overall. This review outlines definitions and diagnostic criteria, risk factors for, and mechanisms of Perioperative Neurocognitive Disorders and offers strategies for preoperative screening and perioperative prevention and management of neurocognitive complications.
Evaluation of the Diagnostic Value of Cell Population Data in Sepsis in Comparison to Localized Infection, Chronic Inflammation, and Noninfectious Inflammation Cases

Introduction Sepsis, defined as an increase of 2 points or more in the sequential organ failure assessment score, is a life-threatening organ dysfunction caused by the dysregulated host response to infection. Volume-conductivity-scatter (VCS) parameters of cell counters which are known as cell population data (CPD) have been suggested to be beneficial in diagnosing sepsis. We aimed to evaluate the diagnostic value of CPD parameters in sepsis in comparison to nonsystemic infection cases (NSI) and non-infectious acute and chronic inflammatory conditions. Materials and Methods We prospectively included four groups of patients” data: sepsis (n = 66), localized infection (pneumonia, n = 59), chronic inflammation (rheumatoid arthritis, n = 92) and noninfectious inflammation (coronary artery bypass graft operation, n = 56) groups, according to their clinical status and laboratory results. Samples for cell counting and serum markers were collected on the same day of culture collection. VCS parameters were measured by Unicel DxH800 Coulter Cellular Analyzer (Beckman Coulter, USA). Results Mean neutrophil volume (MN-V-NE), was highest in the sepsis group [155(149-168)] compared to the localized infection [148(140-158)], chronic inflammation [144.5(142-149)] and noninfectious inflammation [149(145.2-153.7)] (P = 0.001, P < 0.001, P < 0.001, respectively). Neutrophil volume SD (SD-V-NE) was higher in the sepsis [21(18.8-23.7)], significantly differentiating sepsis from other groups. The area under curves of procalcitonin and hs-C-reactive protein were 0.846 and 0.837, respectively, in the receiver-operating characteristic curves (ROC) . CPD combinations, (SD-V NE + SD-V LY + SD-V MO), (SD-V NE + SD-V MO), and (MN-V NE + SD-V NE + SD-C LY + SD-V MO) had greater AUC values than procalcitonin’s. Conclusion VCS parameters might be promising for differentiating sepsis and non-sepsis cases. Additionally, obtaining these data routinely makes their prospects promising without any additional cost and time.
Chemical Space Exploration with Active Learning and Alchemical Free Energies

Drug discovery can be thought of as a search for a needle in a haystack: searching through a large chemical space for the most active compounds. Computational techniques can narrow the search space for experimental follow up, but even they become unaffordable when evaluating large numbers of molecules. Therefore, machine learning (ML) strategies are being developed as computationally cheaper complementary techniques for navigating and triaging large chemical libraries. Here, we explore how an active learning protocol can be combined with first-principles based alchemical free energy calculations to identify high affinity phosphodiesterase 2 (PDE2) inhibitors. We first calibrate the procedure using a set of experimentally characterized PDE2 binders. The optimized protocol is then used prospectively on a large chemical library to navigate toward potent inhibitors. In the active learning cycle, at every iteration a small fraction of compounds is probed by alchemical calculations and the obtained affinities are used to train ML models. With successive rounds, high affinity binders are identified by explicitly evaluating only a small subset of compounds in a large chemical library, thus providing an efficient protocol that robustly identifies a large fraction of true positives.
Matching des Beckenregisters DGU mit dem TraumaRegister DGU

Abstract Background. Complex pelvic traumas, i.e., pelvic fractures accompanied by pelvic soft tissue injuries, still have an unacceptably high mortality rate of about 18%. Patients and methods. We retrospectively evaluated an intersection set of data from the TraumaRegister DGU® and the German Pel-vicInjuryRegisterfrom2004–2009.Patientswith complex and noncomplex pelvic trau-mas were compared regarding their vital pa-rameters, emergency management, stay in the ICU, and outcome.Results. From a total of 344 patients with pelvicinjuries,21%ofpatientshadacom-plex and 79% a noncomplex trauma. Com-plex traumas were significantly less likely to survive (16.7% vs. 5.9%). Whereas vital pa-rameters and emergency treatment in the preclinical setting did not differ substantial-ly, patients with complex traumas were more often in shock and showed acute traumat-ic coagulopathy on hospital arrival, which re-sulted in more fluid volumes and transfu-sions when compared to patients with non-complex traumas. Furthermore, patients with complex traumas had more complications andlongerICUstays.Conclusion. Prevention of exsanguination and complications like multiple organ dys-function syndrome still pose a major chal-lenge in the management of complex pel-vic traumas.
Chelate assisted phytoextraction for effective rehabilitation of heavy metal(loid)s contaminated lands

Abstract The contamination of lands and water by heavy toxic metal(loid)s is an environmental issue that needs serious attention as it poses a major threat to public health. The persistence of heavy metals/metalloids in the environment as well as their potentially dangerous effects on organisms underpins the need to restore the areas contaminated by heavy toxic metal(loid)s. Soil restoration can be achieved through a variety of different methods. Being more cost-effective and environmentally sustainable, phytoremediation has recently replaced traditional processes like soil washing and burning. Many plants have been intensively explored to eliminate various heavy metals from polluted soils through phytoextraction, which is a commonly used phytoremediation approach. The ability of chelants to enhance phytoextraction potential has also received wide attention owing to their ability to elevate the efficiency of plants in removing heavy metal(loid)s. Chelants have been found to improve plant growth and the activity of the defense system. Several chelants, either non-biodegradable or biodegradable, have been reported to augment the phytoextraction efficiencies of various plants. The problem of the leaching of heavy metal(loid)s and secondary pollution caused by non-biodegradable chelants can be overcome by the use of biodegradable chelants to an extent. This review is a brief report focusing on recent articles on chelate-assisted phytoextraction of heavy metal (loids) As, Cd, Cu, Cr, Hg, Ni, Pb, U, and Zn. NOVELTY STATEMENT The review “Chelate assisted phytoextraction for effective rehabilitation of heavy metal(loid)s contaminated land” elaborates on the chelated assisted phytoextraction of eight metals and one metalloids along with their effective chelants.
[99mTc]Tc‐HYNIC‐EcgDf21: A defensin short analogue with potential application in infection foci imaging

Opportunistic infections are a problem of great relevance in public health and the precise detection and localization of infection in the early stages of the disease is of great importance for patient management as well as cost containment. Our proposal seeks to contribute to developing a new agent that meets the needs of diagnosis and follow‐up of fungal and bacterial infections, focused on the design of a radiotracer with the potential for recognition of hidden infection foci. Defensins are plant antimicrobial peptides that not only show activity against plant pathogens but also against human ones. A short analogue of EcgDf1 defensin, EcgDf21d (NH2‐ERFTGGHCRGFRRRCFCTKHC‐COOH), was labelled through the formation of a 99mTc‐HYNIC complex which was assessed for physicochemical and biological behaviour both in vitro and in vivo. The [99mTc]Tc‐HYNIC‐EcgDf21 labelling procedure rendered a single product with remarkably high RCP and stability in the labelling milieu. The Log p value indicated that [99mTc]Tc‐HYNIC‐EcgDf21 has a hydrophilic behaviour, confirmed by the biodistribution profiles. The optimal uptake value was obtained for Candida albicans infection model reaching a lesion/muscle ratio of 3, this correlates with in vitro binding studies, and the lesion can be definitely observed in the scintigraphic images.
PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer

ABSTRACT The tumor recurrence and drug resistance of hepatocellular carcinoma (HCC) threatened patients a lot. The mechanism should be further explored. The information of expression status and survival were available in public databases. The Western blot and immunohistochemistry staining displayed the level of related proteins. CCK-8, colony-formation assays, transwell assay and wound healing assay were performed to illustrate the ability of tumor growth, invasion and migration. In vivo model was established to verify our cell experiments. In our study, we revealed that proteasome 26S subunit, non-ATPase 12 (PSMD12) was high expressed in HCC tissues and positive related to the survival. In vitro experiments suggested that PSMD12 knockdown attenuated tumor cell growth, invasion and migration. Moreover, PSMD12 interference blocked the activation of MEK-ERK pathway. The ERK inhibitor could alleviate the tumor-promoting effect in PSMD12-overexpression cells. In addition, kinesin family member 15 (KIF15) was also observed to be highly expressed in HCC and be harmful to the survival. The public database, the images of immunohistochemistry and the western blot illustrated that PSMD12 and KIF15 was positive correlated. KIF15 knockdown impaired tumor progression and tumor-promoting effect of PSMD12. The xenograft models supported the results of cell experiments. In conclusion, PSMD12 could activated MEK-ERK pathway via KIF15 upregulation, thereby promoting tumor progression. Graphical abstract