Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonestrogen-based hormonal therapies for Alzheimer’s disease

Alzheimer’s disease (AD) is becoming increasingly more prevalent worldwide and is a costly, devastating disease. The fact that females are more likely to be diagnosed with AD than men has contributed to the large amount of research and literature on estrogen’s ability to rescue cognitive decline in aging females. However, recent results from the Women’s Health Initiative Memory Study (WHIMS) and the Research into Memory, Brain Function and Estrogen Replacement (REMEMBER) study, in which estrogen-replacement therapy is shown not to be beneficial to cognition in postmenopausal women, especially in women of more advanced ages, have opened the study of hormones and hormone-based therapies beyond that of sex steroids. As such, recent findings, and the focus of this review, indicate that gonadotropins such as luteinizing hormone have a role on cognitive function and AD. It is likely that the interplay of age, and the timing of estrogen and these other less studied hormones will allow us to gain a better underst.
The stereological ratio of stromal/parenchymal components in postnatal prostate tissue of rats prenatally treated with diclofenac sodium

Since diclofenac sodium extends the pregnancy and affects the fetus, our study aimed to stereologically investigate the components of the rat prostate with prenatally treated with diclofenac sodium. The rats were left overnight to mate. Pregnant animals were kept in a room tempreture with normal light and dark cycles and fed with normal diet. After injections to sham and treated groups for 15 days, 18 male offsprings were housed in three groups (6 placebo; 6 control; 6 treated). The 20 weeks-old animals were perfused and the prostates removed and embedded in paraffin. Tissue sections at 5μm thickness were taken at regular intervals and stained with Hematoxylin-eosin and Masson trichrome. Cavalieri principle was used for volume fractions analysis. Stereological examination revealed 55% acinar epitelium and 45% connective tissue in both control and placebo groups, as well as 60% acinar epitelium and 40% connective tissue in the treated group. Prenatally applied diclofenac sodium did not cause a statistically significant change in the prostate stroma parenchymal ratio in 20-week old rats compared to the control animals (p>0.05).
A high-coverage Neandertal genome from Vindija Cave in Croatia

Revelations from a Vindija Neandertal genome Neandertals clearly interbred with the ancestors of non-African modern humans, but many questions remain about our closest ancient relatives. Prüfer et al. present a 30-fold-coverage genome sequence from 50,000- to 65,000-year-old samples from a Neandertal woman found in Vindija, Croatia, and compared this sequence with genomes obtained from the Altai Neandertal, the Denisovans, and ancient and modern humans (see the Perspective by Bergström and Tyler-Smith). Neandertals likely lived in small groups and had lower genetic diversity than modern humans. The findings increase the number of Neandertal variants identified within populations of modern humans, and they suggest that a larger number of phenotypic and diseaserelated variants with Neandertal ancestry remain in the modern Eurasian gene pool than previously thought. Science, this issue p. 655; see also p. 586 A second deep-sequenced Neandertal genome reveals more about Neandertals and their relationships with ancient humans. To date, the only Neandertal genome that has been sequenced to high quality is from an individual found in Southern Siberia. We sequenced the genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, to ~30-fold genomic coverage. She carried 1.6 differences per 10,000 base pairs between the two copies of her genome, fewer than present-day humans, suggesting that Neandertal populations were of small size. Our analyses indicate that she was more closely related to the Neandertals that mixed with the ancestors of present-day humans living outside of sub-Saharan Africa than the previously sequenced Neandertal from Siberia, allowing 10 to 20% more Neandertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases.
Environmental dynamics during the onset of the Middle Stone Age in eastern Africa

The Middle Stone Age in Africa The Olorgesailie basin in the southern Kenya rift valley contains sediments dating back to 1.2 million years ago, preserving a long archaeological record of human activity and environmental conditions. Three papers present the oldest East African evidence of the Middle Stone Age (MSA) and elucidate the system of technology and behavior associated with the origin of Homo sapiens. Potts et al. present evidence for the demise of Acheulean technology that preceded the MSA and describe variations in late Acheulean hominin behavior that anticipate MSA characteristics. The transition to the MSA was accompanied by turnover of large mammals and large-scale landscape change. Brooks et al. establish that ∼320,000 to 305,000 years ago, the populations in eastern Africa underwent a technological shift upon procurement of distantly sourced obsidian for toolmaking, indicating the early development of social exchange. Deino et al. provide the chronological underpinning for these discoveries. Science, this issue p. 86, p. 90, p. 95 Changes in fauna, landscapes, and climate were associated with novel adaptive behaviors in the earliest Homo sapiens. Development of the African Middle Stone Age (MSA) before 300,000 years ago raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens. We used temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a markedly different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. Aspects of Acheulean technology in this region imply that, as early as 615,000 years ago, greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.
Reversibility of citrate synthase allows autotrophic growth of a thermophilic bacterium

About-face for citrate synthase Classically, it is thought that citrate synthase only works in one direction: to catalyze the production of citrate from acetyl coenzyme A and oxaloacetate in the tricarboxylic acid (TCA) cycle. The TCA cycle can run in reverse to cleave citrate and fix carbon dioxide autotrophically, but this was thought to occur only with alternative enzymes, such as citrate lyase. Now Nunoura et al. and Mall et al. have discovered thermophilic bacteria with highly efficient and reversible citrate synthase that requires reduced ferredoxin (see the Perspective by Ragsdale). This function is undetectable by metagenomics, but classical biochemistry filled in the gaps seen between the genome sequences and the phenotypes of the organisms. The direction of catalysis depends on the availability of organic versus inorganic carbon and reflects a flexible bet-hedging strategy for survival in fluctuating environments. In evolutionary terms, this capacity might predate the classical TCA cycle and is likely to occur in a wide range of anaerobic microorganisms. Science, this issue p. 559, p. 563; see also p. 517 Classical biochemistry reveals the occurrence of an unexpected capacity to reverse the tricarboxylic acid cycle in anaerobic microbes. Biological inorganic carbon fixation proceeds through a number of fundamentally different autotrophic pathways that are defined by specific key enzymatic reactions. Detection of the enzymatic genes in (meta)genomes is widely used to estimate the contribution of individual organisms or communities to primary production. Here we show that the sulfur-reducing anaerobic deltaproteobacterium Desulfurella acetivorans is capable of both acetate oxidation and autotrophic carbon fixation, with the tricarboxylic acid cycle operating either in the oxidative or reductive direction, respectively. Under autotrophic conditions, the enzyme citrate synthase cleaves citrate adenosine triphosphate independently into acetyl coenzyme A and oxaloacetate, a reaction that has been regarded as impossible under physiological conditions. Because this overlooked, energetically efficient carbon fixation pathway lacks key enzymes, it may function unnoticed in many organisms, making bioinformatical predictions difficult, if not impossible.
Compressive Optic Neuropathy Secondary to Sphenoid Sinus Aspergillosis

The authors report a case of retrobulbar optic neuropathy caused by noninvasive isolated sphenoid sinus aspergillosis. A 62-year-old woman suffered from left temporal headache with progressive visual loss in the left eye. Relative afferent pupillary defect, normal appearance of optic disc, and elevated erythrocyte sedimentation rate were found. Under the impression of posterior ischemic optic neuropathy caused by giant cell arteritis, urgent pulse therapy with corticosteroids was administered. Later, endoscopic sphenoid sinus surgery was undertaken following computed tomography and magnetic resonance imaging, which demonstrated a heterogenous mass lesion in the left sphenoid sinus. A fungal ball was removed from the sphenoid sinus, and acute-angled branching, septate hyphae were seen on pathological examination. Fungus culture grew Aspergillus fumigatus. The patient's best-corrected visual acuity improved to 20/400 in the left eye after a six-month follow-up period.
Heart transplantation in insulin–treated diabetic patients with diabetes–related complications

Heart transplantation is the most effective therapy for end‐stage heart failure in patients with diabetes mellitus (DM). However, diabetes‐related complications (DRCs) are a relative contraindication for heart transplantation. Nevertheless, the increasing prevalence of both DM and congestive heart failure makes it necessary to perform heart transplantation even in those patients with advanced DM. We performed a retrospective analysis on long‐term survival in 47 patients with insulin‐treated DM and DRCs (group 1). Survival rate and causes of death were compared with data of a group of heart transplant recipients without DM (n = 1061, group 2). Mean follow‐up time of all heart transplant recipients was 68.2 months (range: 0–204 months). Overall mortality during follow‐up was 42.9%. Long‐term survival did not differ significantly between study groups, but tended to be shorter in group 1 than in group 2 (P = 0.07). In group 1, steroid‐free immunosuppressive therapy was associated with a higher percentage of long‐term survivors compared with no steroid‐free immunosuppression. Our data demonstrate that long‐term survival is acceptable in heart transplant recipients with preoperatively diagnosed DM and DRCs. Consequently, advanced DM should no longer be a relative contraindication for heart transplantation.
Fibril structure of amyloid-β(1–42) by cryo–electron microscopy

Elucidating pathological fibril structure Amyloid-β (Aβ) is a key pathological contributor to Alzheimer's disease. Gremer et al. used cryoelectron microscopy data to build a high-quality de novo atomic model of Aβ fibrils (see the Perspective by Pospich and Raunser). The complete structure reveals all 42 amino acids (including the entire N terminus) and provides a structural basis for understanding the effect of several disease-causing and disease-preventing mutations. The fibril consists of two intertwined protofilaments with an unexpected dimer interface that is different from those proposed previously. The structure has implications for the mechanism of fibril growth and will be an important stepping stone to rational drug design. Science, this issue p. 116; see also p. 45 Cryo–electron microscopy structure of an amyloid-β(1–42) fibril reveals a protofilament interface and the entire N-terminal region. Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer’s disease patients. We present the structure of an Aβ(1–42) fibril composed of two intertwined protofilaments determined by cryo–electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall “LS”-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed “groove” and “ridge,” leading to different binding pathways on both fibril ends, which has implications for fibril growth.
Relation of Red Cell Distribution Width With CHA2DS2-VASc Score in Patients With Nonvalvular Atrial Fibrillation

Background: Red cell distribution width (RDW) has been shown to be helpful in predicting adverse long-term events in patients with cardiovascular diseases. However, to date, no study has been conducted on the relationship between RDW and thromboembolism risk in atrial fibrillation (AF). Therefore, we aimed to investigate the relationship between RDW and CHA2DS2-VASc score used for the evaluation of thromboembolism risk in patients with AF. Methods: The study population consisted of 320 patients with AF. We calculated CHA2DS2-VASc risk score for each patient and baseline hemoglobin, white blood cell, RDW, mean platelet volume, platelet counts, estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), and left atrial volume index (LAVi) were measured. Results: High CHA2DS2-VASc score group had higher RDW, lower LVEF, higher LAVi, and lower eGFR values when compared to the low CHA2DS2-VASc score group. The multivariate logistic regression analysis performed to predict high CHA2DS2-VASc scores revealed that RDW eGFR, LVEF, and LAVi were independent predictors. The area under the receiver–operating characteristic curve of RDW was 0.65 (0.59-0.71, P < .001) to predict high CHA2DS2-VASc score. Conclusion: Our study results indicate that RDW values are significantly correlated with CHA2DS2-VASc score in nonanemic patients with AF, while also being independent predictor of high CHA2DS2-VASc score.
Arabidopsis pollen tube integrity and sperm release are regulated by RALF-mediated signaling

Timing a switch in tissue integrity In plants, sperm cells travel through the pollen tube as it grows toward the ovule. Successful fertilization depends on the pollen tube rupturing to release the sperm cells (see the Perspective by Stegmann and Zipfel). Ge et al. and Mecchia et al. elucidated the intercellular cross-talk that maintains pollen tube integrity during growth but destroys it at just the right moment. The signaling peptides RALF4 and RALF19, derived from the pollen tube, maintain its integrity as it grows. Once in reach of the ovule, a related signaling peptide, RALF34, which derives from female tissues, takes over and causes rupture of the pollen tube. Science, this issue p. 1596, p. 1600; see also p. 1544 A suite of signaling peptides and their receptors regulate tissue stability as the pollen tube navigates toward the ovule. In flowering plants, fertilization requires complex cell-to-cell communication events between the pollen tube and the female reproductive tissues, which are controlled by extracellular signaling molecules interacting with receptors at the pollen tube surface. We found that two such receptors in Arabidopsis, BUPS1 and BUPS2, and their peptide ligands, RALF4 and RALF19, are pollen tube–expressed and are required to maintain pollen tube integrity. BUPS1 and BUPS2 interact with receptors ANXUR1 and ANXUR2 via their ectodomains, and both sets of receptors bind RALF4 and RALF19. These receptor-ligand interactions are in competition with the female-derived ligand RALF34, which induces pollen tube bursting at nanomolar concentrations. We propose that RALF34 replaces RALF4 and RALF19 at the interface of pollen tube–female gametophyte contact, thereby deregulating BUPS-ANXUR signaling and in turn leading to pollen tube rupture and sperm release.
Pulmonary Embolism and Deep Venous Thrombosis Following Laparoscopic Cholecystectomy

There is considerable uncertainty related to the thromboembolic risk after laparoscopic cholecystectomy. Patients with pulmonary embolism (PE), deep venous thrombosis (DVT), or venous thromboembolism (VTE) at hospital discharge following laparoscopic cholecystectomy were identified from the Nationwide Inpatient Sample. From 1998 through 2009, 4 107 430 laparoscopic cholecystectomies were performed. The in-hospital prevalence of PE was 0.15%, DVT was 0.40%, and VTE was 0.53%. The prevalence of PE increased from 0.04% in patients aged 21 to 30 years to 0.31% in patients aged 71 to 80 years. Deaths due to in-hospital PE were 780 (0.02%) of the 4 107 430 laparoscopic cholecystectomies. The rate of death increased with age. The prevalence of VTE following laparoscopic cholecystectomy is low and fatal PE is rare. The risk of VTE increased with age, as did the risk of death in those who had PE. These data may be useful in assessing the use of thromboprophylaxis in patients undergoing laparoscopic cholecystectomy.
Risk Assessment to Predict Arterial and Venous Events in Patients Undergoing Percutaneous Coronary Intervention

Atherosclerosis and venous thromboembolism (VTE) share common risk factors. We set to assess the strength of the association between atherosclerosis risk factors and disease manifestation, and VTE, in patients with coronary artery disease undergoing percutaneous coronary intervention. We pooled data from 6 global randomized controlled trials assessing coronary stenting (ENDEAVOR and SIRIUS programs), developed separate risk scores to predict major adverse cardiac and cerebrovascular events (MACCEs: cardiac death, myocardial infarction, and stroke) and VTE, and compared their performance. The 5-year rates of MACCE and VTE were 10.8% and 2.04%, respectively. Selected predictors for MACCE performed equally well in predicting VTE (area under the receiver–operating characteristic curve [AUC] 0.651 vs 0.672), and selected predictors for VTE performed equally well in predicting MACCE (AUC 0.699 vs 0.620). Ejection fraction and age were associated with both MACCE and VTE. These findings support the concept of overlapping pathophysiology of VTE and atherothrombosis.
Video-Based Outdoor Human Reconstruction

A human body scanning system of great practical convenience, which can be used in an outdoor environment, is proposed. The system uses only a single conventional video camera without the aid of special sensors or controlled illuminations. We leverage the structure from motion calibration results directly and improve the available video-based dense 3D reconstruction by integrating the surface smoothness constraints. The point cloud reinforcement is proposed to detect and adjust the conflict point data for the slender and shaky body parts. Combined with the silhouette adaptation, the proposed point cloud reinforcement achieves reasonable and plausible mesh reconstruction on these challenging parts. We further introduce the close-shot frames to refine the prereconstructed mesh model, leading to a colored watertight model. The overall system is approximate to automatic since only one or two times of painting brush interaction are required for robust and high-quality multiview image segmentation. The experiment results on various test sequences demonstrate the effectiveness and the robustness of the proposed method, even under very challenging scenarios when shaking body, varying illumination, and textureless regions occur.
Accelerating Vanishing Point-Based Line Sampling Scheme for Real-Time People Localization

In advanced video surveillance systems, people localization is usually a part of the complete system and should be accomplished in a short time so as to reserve sufficient processing time for subsequent high-level analysis, such as abnormal event/behavior detection and intruder detection. Hence, in addition to localization accuracy, computational efficiency is of critical importance as well. In this paper, we adopt a vanishing point-based line sampling scheme and propose a fast multicamera people localization approach capable of locating a crowd of dense people and estimating their heights in a fairly short time with high accuracy. For each camera view, sample lines, originated from a vanishing point, of foreground objects are projected onto the ground plane. Then, people locations are estimated by detecting the ground regions containing a high density of the projected lines. Enhanced from some previous works, the proposed approach does not require processing steps of high computation cost, such as projecting all foreground pixels of all views to multiple reference planes or computing pairwise intersections of projected sample lines at different heights. In addition, some novel acceleration modules, such as torso validation and physical rule-based filtering, are developed to further reduce the computation time of people localization. The experiments on real surveillance scenes validate that the proposed approach achieves significant speedup (up to 186%) over state-of-the-art techniques while still ensure a comparably high localization accuracy, even for crowded scenes with serious occlusions.
A XML query results ranking approach based on probabilistic information retrieval model

This paper proposes an automated ranking approach based on probabilistic information retrieval model. Firstly, based on the XML data and query history, this approach takes advantage of the probabilistic information retrieval model to capture the correlations between the unspecified and specified values of leaf nodes as well as the user preferences, and then constructs the scoring function and ranks the query results according to the ranking scores. Results of experiments demonstrate that ranking method proposed can meet the user's needs and preferences effectively.
Neurons that drive and quench thirst

Median preoptic neurons modulate water intake and the urge to drink Thirst is a vital primordial emotion that motivates fluid intake to compensate for incessant water loss incurred as a result of breathing, sweating, and urine production. Indeed, the maintenance of adequate hydration is a prerequisite for life and, accordingly, the desire to drink emerges as soon as the body's water content declines by 1 to 2%, and this feeling intensifies progressively with further depletion (1–3). Although regions in the brain that are critical for water intake have been known for more than 60 years, the identification and functional analysis of thirst-related neurons only became possible with the recent advent of genetically targeted photoactivation and photometry, methods that respectively allow manipulation and monitoring of electrical activity in vivo, using fiber-optic microprobes (4–7). On page 1149 of this issue, Allen et al. (8) reveal the existence of neurons that specifically encode the intensity and aversive quality of thirst within the median preoptic nucleus (MnPO) of the hypothalamus.