bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study on the Application of Robotic Hair Restoration Technology Versus Traditional Follicular Unit Excision in Male Androgenetic Alopecia
Authors: Zhu Yifei , Yang Kai , Lin Jui‐Ming , Ni Chunya , Zhang Yue , Li Zheng , Liu Qingmei , Zhou Yinghui , Lin Jinran , Wu Wenyu
Published: September 2024

Background

The robotic hair transplant technology, ARTAS, has a series of fine mechanical structure and an intelligent recognition system that allows it to independently select hair follicular units (FUs) and effectively harvest hair. After entering China in 2016, ARTAS has attracted the attention of hair transplant surgeons and hair loss patients given its advantages in a short learning curve and simple operation.

Objective

To compare the efficacy and safety between the ARTAS system and follicular unit excision (FUE) in the treatment of male androgenetic alopecia (AGA) and to further promote the improvement and upgrading of ARTAS technology concerning hair transplantation.

Methods

Thirteen Chinese male patients with Norwood–Hamilton II–IV AGA aged 25–35 years were enrolled in this study. The donor site of each patient was randomly divided into left and right regions, receiving ARTAS on one side and FUE on the other. Yield, transection, and discard rates of hair FUs from both sides were compared. Safety of the procedures in whole, as well as follow‐up results were investigated and evaluated.

Results

The total yield rate on the ARTAS side was lower than on the FUE side (82.05% vs. 90.03%, p > 0.05); the total discard rate on the ARTAS side was higher than on the FUE side (10.71% vs. 5.46%, p < 0.05); the total transection rate on the ARTAS side was lower than on the FUE side (13.17% vs. 13.96%, p > 0.05). No significant difference was found in patient satisfaction (efficacy), and no side effects or complications were detected during or after all surgeries.

Conclusion

The current iteration of Robotic hair transplant technology is effective and safe, and can be recommended for AGA hair transplantation surgery.
Diagnosis of high‐speed railway ballastless track arching based on unsupervised learning framework
Authors: Tang Xueyang , Wang Yi , Cai Xiaopei , Yang Fei , Hou Yue
Published: September 2024

Vehicle‐mounted detection methods have been widely applied in the maintenance of high‐speed railways (HSRs), providing feasibility for diagnosing ballastless track arching. However, applying detection data faces several key limitations: (1) The threshold mostly requires manual setting, making recognition accuracy highly subjective; (2) the extensive workload of manual inspections makes it challenging to label detection data, hindering the application of supervised learning approaches. To address these problems, this paper utilizes the longitudinal level irregularity data obtained from vehicle‐mounted detection, employing the concept of unsupervised learning for dimensionality reduction, combined with clustering algorithms and minimal label fine‐tuning, to design two frameworks: the fully unsupervised framework (FUF) and the few‐shot fine‐tuned framework (FFF). Experiments on dynamic detection data from a Chinese HSR line were conducted, comparing the performance of data dimensionality reduction, clustering, and classification under different strategy combinations. The results show that the improved variational autoencoder significantly enhances the performance of the encoder in dimensionality reduction, facilitating better feature extraction; the FUF achieves effective clustering outcomes without any labeled samples and its adjusted rand index score exceeded 0.8, showcasing its robustness and applicability in scenarios with no prior annotations; the FFF requires only a small number of labeled samples (labeling ratio of 5%) and achieves excellent performance, with metrics such as accuracy exceeding 0.85, thus greatly reducing the reliance on labeled data. This study offers a novel method for solving engineering issues with limited labeled data, providing an efficient solution for identifying track arching defects and advancing railway infrastructure monitoring.
Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity
Authors: Mechanick Jeffrey I. , Butsch W. Scott , Christensen Sandra M. , Hamdy Osama , Li Zhaoping , Prado Carla M. , Heymsfield Steven B.
Published: September 2024

The rapid and widespread clinical adoption of highly effective incretin‐mimetic drugs (IMDs), particularly semaglutide and tirzepatide, for the treatment of obesity has outpaced the updating of clinical practice guidelines. Consequently, many patients may be at risk for adverse effects and uncertain long‐term outcomes related to the use of these drugs. Of emerging concern is the loss of skeletal muscle mass and function that can accompany rapid substantial weight reduction; such losses can lead to reduced functional and metabolic health, weight cycling, compromised quality of life, and other adverse outcomes. Available evidence suggests that clinical trial participants receiving IMDs for the treatment of obesity lost 10% or more of their muscle mass during the 68‐ to 72‐week interventions, approximately equivalent to 20 years of age‐related muscle loss. The ability to maintain muscle mass during caloric restriction‐induced weight reduction is influenced by two key factors: nutrition and physical exercise. Nutrition therapy should ensure adequate intake and absorption of high‐quality protein and micronutrients, which may require the use of oral nutritional supplements. Additionally, concurrent physical activity, especially resistance training, has been shown to effectively minimize loss of muscle mass and function during weight reduction therapy. All patients receiving IMDs for obesity should participate in comprehensive treatment programs emphasizing adequate protein and micronutrient intakes, as well as resistance training, to preserve muscle mass and function, maximize the benefit of IMD therapy, and minimize potential risks.
Local Regulatory Changes of HSD11B1 and NR3C1 in the Follicular and Luteal Tissue During Experimentally Induced Ovulation in the Cow
Authors: Berisha Bajram , Pfaffl Michael W. , Thaqi Granit
Published: September 2024

The objective of the study was to characterise the expression patterns of the two key components of cortisol action namely HSD11B1 (11‐beta‐hydroxysteroid dehydrogenase type 1) and NR3C1 (nuclear receptor subfamily 3, group C, member 1, also known as the glucocorticoid receptor) in superovulation induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. Bovine ovaries containing preovulatory follicles or CL were timely defined during induced ovulation as follows: 0 h before GnRH (Gonadotropin‐releasing hormone) application, and 4, 10, 20, 25 (follicles) and 60 h (early CL) after GnRH. The low mRNA expression of HSD11B1 and NR3C1 in the follicle group before the GnRH application increased significantly in the follicle group 20 h after GnRH and remained high afterward also in the early CL group. In contrast, the high NR3C1 mRNA decreased in follicles 25 h after GnRH (close to ovulation) and significantly increased again after ovulation (early CL). Our results indicated the involvement of HSD11B1 and NR3C1 as the two key components of cortisol action in the local mechanisms coordinating final follicle maturation, ovulation, follicular‐luteal transition and CL development in the cow.
LncRNA SLNCR1 facilitates angiogenesis and tumor growth in melanoma via DNMT1‐mediated epigenetically silencing SPRY2
Authors: Li Ke , Wu Lijun , Jiang Jingting
Published: September 2024

Background

The malignancy of melanoma is attributed to its pronounced invasiveness, extensive vascularization, and rapid tumor cell growth and metastasis. LncRNA SLNCR1 is closely associated with a variety of aggressive tumors. However, our understanding of SLNCR1 influences on malignant melanoma growth metastasis mechanism especially proangiogenic mechanism remains unclear.

Methods

The expression of SLNCR1 was evaluated in melanoma tissues, adjacent tissues, melanoma cell lines. The abilities of SLNCR1 on proliferation, migration, and angiogenesis of HUVECs were detected by CCK‐8, flow cytometry, and Western blot assays. The association between SLNCR1, DNMT1, and SPRY2 was assessed by ChIP, RIP, and Western blot assays. The effect of SLNCR1 on tumor growth was determined using a xenograft model in nude mice.

Results

SLNCR1 was confirmed to be highly expressed in melanoma tissues and cells. CM from melanoma cells transfected with sh‐SLNCR1 attenuated proliferation, migration, and angiogenesis of HUVECs. Moreover, loss of SLNCR1 hindered tumor growth and metastasis, as evidenced by reduced tumor size and weight, as well as angiogenesis. Mechanistic studies revealed that SLNCR1 silenced SPRY2 expression, likely through enhancing DNMT1‐mediated DNA methylation of SPRY2 promoter.

Conclusion

SLNCR1 is an oncogene that interacts with DNMT1 to mediate SPRY2 methylation, thereby suppressing SPRY2 expression and promoting the angiogenesis and tumor growth in melanoma. SLNCR1 may serve as a potential target for melanoma treatment.
An artificial intelligence powered study of enlarged facial pore prevalence on one million Chinese from different age groups and its correlation with environmental factors
Authors: Zhou Huanjun , Xie Hang , Wu Liang , Song JinYan , Ma Zitao , Zeng Danning , Wang Xiaodi , Shi Su , Qu Yulan , Luo Yajun , Meng Xia , Niu Yue , Kan Haidong , Cao Jian , Pernodet Nadine
Published: September 2024

Background

Enlarged pores are amidst one of the top cosmetic concerns, especially among Chinese. Many small‐group studies have been conducted in understanding their prevalence and beauty relevance. Nonetheless, population‐level investigations are still lacking because of gaps in data collection and processing of large‐scale studies. Owing to the recent technological advancement enabled by artificial intelligence, databases on the scale of millions can be processed and analyzed readily.

Materials and methods

Powered by big data capabilities, revealed a number of novel trends on pore conditions among over‐a‐million Chinese participants recruited via the “You Look Great Today” mobile application. A scoring model was constructed, which demonstrated high consistency with conventional grading method from dermatologists. Environmental data (weather, air pollution, light at night satellite) were applied to correlate with pore severity.

Results

Intraclass correlations between the two scoring systems were strong, with coefficients ranging from 0.79 to 0.92 for different facial areas. Statistical differences in pore severity among all four facial areas (cheek, forehead, nose, and overall) were observed, with the cheek exhibiting the most severe pore condition. Interestingly, Chinese men suffer from more severe pore condition than females. Multiple environmental factors exhibited strong correlations with cheek pore severity and were statistically fitted into linear regressions. Specifically, incremental risk with Each Low Temperature, Low Humidity, And High Solar Exposure correlate to worse cheek pore conditions. Although the Pearson correlation was low between cheek pore severity and light at night, comparison between representative cities demonstrated that in geologically similar cities, higher light at night corresponds to more severe cheek pore conditions.

Conclusion

Our study is showcasing a robust and reliable AI model in facial pore evaluation. More importantly, insights uncovered using this facile approach also bear significant cosmetic ramifications in treatment of pore enlargement.
Lactate increases ADAM10 activity and reduces BACE1 activity in mouse brain
Authors: Moberg Isabel , McCarthy Seth F. , Bellaflor Sarah , Finch Michael S. , Hazell Tom J. , MacPherson Rebecca E. K.
Published: September 2024

The accumulation and aggregation of beta‐amyloid (Aβ) peptides contributes to neuronal dysfunction and death. These Aβ peptides originate from a transmembrane protein known as amyloid precursor protein (APP), which can be processed via two competing pathways. Alpha‐secretase (ADAM10) cleavage is thought to be neuroprotective while beta‐secretase (BACE1) cleavage results in the production of Aβ. Aerobic exercise reduces BACE1 activity, but the mechanisms involved are unknown though several exercise‐induced mediators such as lactate may be involved. The current study examined whether systemic lactate can alter APP processing and BACE1 and ADAM10 activity. Mice were randomly assigned to one of four groups (n = 10 per group): (1) sedentary; (2) lactate‐injection (1.0 g kg−1 body mass); (3) exercise; and (4) exercise and oxamate (lactate dehydrogenase inhibitor; 750 mg kg−1 body mass). Two hours following intervention, the hippocampus and prefrontal cortex (PFC) were collected. In the PFC lactate‐injection and exercise resulted in higher ADAM10 activity compared to sedentary (exercise P = 0.0215, lactate P = 0.0038), in the hippocampus lactate‐injection was higher compared to sedentary (lactate P = 0.011), and this was absent in the presence of oxamate. Hippocampal BACE1 activity was lower in the lactate group compared to the exercise group (P = 0.01). Oxamate resulted in higher BACE1 protein content compared to sedentary in the PFC (vs. sedentary P = 0.048). These findings suggest that lactate is important for regulating ADAM10 activity and thereby shifts APP processing away from Aβ production.

image

Key points

Exercise is known to alter the processing of amyloid precursor protein by reducing the activity of the rate‐limiting enzyme BACE1 and increasing the activity of ADAM10.

It is thought that exercise‐induced factors are responsible for these enzymatic changes.

This study examined if lactate accumulation plays a role in this process.

Mice were assigned to one of four groups: sedentary, lactate, exercise and exercise + lactate.

The findings demonstrate that lactate accumulation alters brain BACE1 and ADAM10 and shifts amyloid precursor protein processing away from beta‐amyloid production.
A New Triangular Thin Shell Element Based on the Absolute Nodal Coordinate Formulation for Complex Surfaces
Authors: Zhang Binghua , Fan Wei , Ren Hui
Published: September 2024

This work proposed a new Hermite triangular thin shell element based on the absolute nodal coordinate formulation to model thin shells with complex curved surfaces. Three techniques are adopted to enhance its universality and efficiency. First, local numerical curvilinear coordinates are used on each node for those curved surfaces whose global curvilinear coordinates cannot be obtained analytically, and the Lie group interpolation is used for obtaining the curvilinear coordinates on the non-nodal domain. Second, the slope vector of the element is obtained by cross-producing the two gradient vectors only on each node; but interpolated inside the element to ensure its continuity. Additionally, this processing maintains the linear relationships between the shape functions and nodal coordinates, resulting in constant elastic tensors. Third, the enhanced assumed strains (EAS) and the assumed natural strains (ANS) methods are adopted respectively to accelerate the convergence speed and avoid locking problems of the element. Several numerical examples show that this new element is universal for irregularly curved surfaces without locking problems. In addition, the efficiency is much higher than the traditional triangular shell element.
An Advanced Sine-Hyperbolic Creep-Damage Model Incorporating Threshold Strength
Authors: Hossain Md Abir , Haque Mohammad Shafinul , Pellicotte Jacob , Stewart Calvin M.
Published: September 2024

This study aims at improving the classic sine-hyperbolic (Sinh) creep-damage model to predict minimum-creep-strain-rate (MCSR), rupture, damage, and creep deformation. The Sinh model employs a continuum-damage-mechanics-based framework to model secondary and tertiary creep regimes. In Sinh, the creep strain and damage rate equations exhibit an implicit threshold stress that arises during numerical optimization. Herein, the Sinh model is modified to include an explicit threshold strength as a material property and the tensile strength. Threshold strength is defined as the lower limit for creep activation at a given temperature. Stresses are applied below the threshold, resulting in infinite life. The advanced Sinh offers several advantages including a physical significance of stress ratios where the onset of creep is defined by threshold strength, a closed-form solution where the rate equations remain finite at any combination of stress and temperature, and adaptability in finite element analysis where the solution space remains numerically stable. Experimental creep data of 304 SS at multiple isotherms are gathered from prior literature. The advanced Sinh is calibrated to the MCSR and SR data of 304 SS. The calibration of threshold strength follows a standard procedure from literature and is observed to be realistic for stainless steel at elevated temperatures. The MCSR and SR predictions illustrate the Sigmoidal bend and demonstrate zero creep rate and infinite life at or below threshold strength. The creep deformation and damage predictions exhibit agreement with experimental data. The advanced Sinh is validated by employing finite element simulation to ensure the applicability of the model across a range of applications. The advanced Sinh improved creep response prediction and added physical realism to the model's framework.
Investigation of the Sigma Approximation Technique for the Solution of the Time Spectral Equation System
Authors: Zhu Yuze , Zhang Yuxuan , Zhang Sen , Wang Dingxi
Published: September 2024

The time spectral method (TSM) is commonly utilized to analyze periodic unsteady flows within turbomachines. However, the time spectral solutions in regions with large temporal and spatial gradients, such as wakes, shocks, and boundary layers, can be plagued with unphysical oscillations, known as the Gibbs phenomenon. This paper presents an investigation into the sigma approximation technique, which is capable of significantly attenuating the Gibbs phenomenon by dampening high-frequency nonlinear components in time spectral solutions. Central to this technique are three sigma parameters: the exponent, the cutoff number, and the number of harmonics, which collectively determine the damping effects for each frequency. However, the optimal combination of them remains to be ascertained considering the tradeoff between the accuracy of solutions and the reduction of unphysical oscillations. In this study, a two-row compressor configuration is first selected, and numerical simulations are performed to evaluate the efficacy of this technique under near-peak efficiency and near-stall operating conditions. It is found that Gibbs-type unphysical oscillations can be effectively mitigated without notably compromising solution accuracy through an optimal combination of sigma parameters. The NASA Stage 35 case study further verifies the effectiveness of the proposed optimal sigma parameter combination in preserving the accuracy of time spectral solutions based on the data from test rig. Moreover, the von Neumann analysis reveals that the sigma approximation technique can enhance the numerical stability of the time spectral equation system, thereby allowing the use of aggressive numerical parameters to accelerate convergence. The stability analysis results are verified by a two-dimensional bump under two different flow conditions and further assessed using the two-row compressor.
Briefe einer Antifaschistin: 1940
Authors: Obermayer August
Published: September 2024

Der Text zeichnet die Ansichten und Erfahrungen von Charlotte Angermann, Einwohnerin von Dresden im ersten Jahr des Zweiten Weltkriegs, auf. Da der Briefverkehr zwischen Deutschland und Großbritannien zu diesem Zeitpunkt abgebrochen war, begann Charlotte ihre Tochter und ihren Schwiegersohn, Marianne und Franz Bielschowsky, in ihrem Tagebuch anzuschreiben. Diese Eintragungen fassen die Hauptereignisse des Jahres 1940 aus der Perspektive einer unpolitischen Frau an der Heimatfront zusammen. Sie schreibt von der schlimmer werdenden Lebensmittelrationierung und den mangelnden Konsumgütern, von Bombenabwürfen auf deutsche Städte und von den ersten Gefallenen unter ihren Bekannten und Familienangehörigen.
The text records the thoughts and experiences of Charlotte Angermann in Dresden in the first year of the Second World War. As there was no postal communication with Great Britain, Charlotte began to address Marianne and Franz Bielschowsky, her daughter and son-in-law, in the form of diary entries as a substitute for letter writing. Charlotte’s journal summarises the main events of 1940 from the point of view of a politically uncommitted woman on the Home Front. She writes of increased rationing, the first bombing raids and of the military deaths of acquaintances and family members.
Letters of an antifascist: 1941
Authors: Barton Peter
Published: September 2024

These texts record daily life under National Socialism during the Second World War as it was experienced by Charlotte Angermann in Dresden. Angermann describes bombing raids on other German cities, the rationing of food and shortages of consumer goods, and the deaths of friends and family members. These short journal entries are written in the form of a direct address to Charlotte’s daughter, Marianne Angermann-Bielschowsky, who lived with her husband, the German-Jewish physician Franz Bielschowsky, in Great Britain where they both worked as researchers at the University of Sheffield.
Letters of an antifascist: 1945
Authors: Barton Peter
Published: September 2024

The text records day to day life under National Socialism as it was experienced by Charlotte Angermann, a resident of Dresden at the end of the Second World War and in the first months after the German capitulation in May 1945. Angermann writes of the bombing of Dresden, the shortages faced by the general population, the deaths of friends and family members and the difficult co-existence with Soviet occupation forces. The diary entries are constructed as an address to her daughter, Marianne Angermann-Bielschowsky, who was at the time in Great Britain where she and her husband, Franz Bielschowsky, worked as researchers with Professor H.N. Green at the University of Sheffield.
Angermann-Beutler Family Tree
Authors: Barton Peter
Published: September 2024

The text is a transcription of the family tree for the Angermann, Beutler and Klemm families found in the back of a diary written by Charlotte Angermann née Beutler, wife of Konrad Angermann and mother of Marianne Angermann-Bielschowsky. Those listed were from long established Saxon families, though some had moved to Rhineland Westfalia at the time the tree was sketched in 1946. Charlotte detailed the family relationships for her daughter, Marianne, in order to show what had become of them as a consequence of the Second World War. Several family members were actively involved in the Nazi Party, the Wehrmacht or SS, while others were antifascists.
Optical properties of 4H-SiC and 6H-SiC from infrared to vacuum ultraviolet spectral range ellipsometry (0.05–8.5 eV)
Authors: Mainali Madan K. , Dulal Prabin , Shrestha Bishal , Amonette Emily , Shan Ambalanath , Podraza Nikolas J.
Published: September 2024

Complex dielectric function (ɛ = ɛ1 + iɛ2) spectra are obtained from reflection mode spectroscopic ellipsometry and unpolarized transmittance measurements for 4H and 6H stacking sequence silicon carbide (SiC) nitrogen-doped single crystals from the infrared (IR) to vacuum ultraviolet (VUV) spectral range. A single parametric model describing ɛ predominately for the ordinary directions is developed over the 0.05–8.5 eV spectral range from analysis of (0001)-oriented back side roughened 4H-SiC and 6H-SiC single crystals with some contribution from the extraordinary direction of 6H-SiC in the IR region. Indirect bandgaps for 4H-SiC and 6H-SiC are found to be 3.30 and 3.03 eV, respectively, and the corresponding direct optical gaps are at 4.46 and 4.42 eV. A model describing the optical response in the IR spectral range is created using a Drude expression and either transverse optical (TO) and longitudinal optical (LO) (TOLO) or Lorentz oscillator models. Free carrier concentration (N) is optically measured to be 3.7 × 1018 and 3.3 × 1018 cm−3 using TOLO and Lorentz oscillator models, respectively, and the corresponding carrier mobility (μ) is 34 and 39 cm2/V s for 4H-SiC. Under the same assumption for 6H-SiC, N is measured to 8 × 1018 cm−3 using either TOLO or Lorentz oscillator models and μ is 9 and 10 cm2/V s using the TOLO and Lorentz oscillator models, respectively, in the ordinary direction and 5 cm2/V s in the extraordinary direction using either model. For 4H-SiC, using the TOLO oscillator model, TO and LO phonon modes are measured at 797.7 and 992.1 cm−1, respectively, and corresponding modes are found at same locations using the Lorentz oscillator model. In 6H-SiC, using the TOLO model, TO modes in ordinary and extraordinary directions are found at 797.7 and 789.7 cm−1, and corresponding modes are at 796.9 and 788.9 cm−1 using the Lorentz oscillator model. The LO modes using the TOLO model are found at 992 and 984 cm−1 in the ordinary and extraordinary directions, respectively, and the same modes in the corresponding direction using the Lorentz oscillator model are located at 975.9 and 967.9 cm−1.
Optical emission spectroscopy as a method for evaluating the change in Si etching structures profile in ICP SF6/C4F8 plasma: Microstructures
Authors: Osipov Artem A. , Fumina Alina E. , Speshilova Anastasia B. , Endiiarova Ekaterina V. , Osipov Armenak A. , Alexandrov Sergey E.
Published: September 2024

In this work, a method for in situ diagnostics of the etching profile of silicon structures (etching window sizes 15–400 μm) using optical emission spectroscopy was proposed. To determine the relationship between the etching profile and plasma parameters, the influence of technological parameters on the etching characteristics (vertical and lateral etching rate, selectivity in relation to photoresist, and sidewall angle) was studied. As a general parameter, which reflects the changes in plasma characteristics depending on the selected technological parameters, the parameter X (C/F ratio in SF6/C4F8 plasma) was introduced. Based on the results obtained, a general pattern between the lateral etching rate, sidewall angle, and optical emission spectra was identified. Thus, ranges of X values, at which the lateral etching rate does not exceed 5 nm/min for 15–30 μm structures and 15 nm/min for 100 μm structures, were estimated: 0.38 ≤ X ≤ 0.77 and 0.28 ≤ X ≤ 0.46, respectively. For 250–400 μm structures, ranges of X values, at which the sidewall angle is acute, straight, and obtuse, were determined: 0.16 ≤ X < 0.29, 0.29 ≤ X ≤ 0.41, 0.41 < X ≤ 0.75, respectively.
Efficient mask optimization for enhanced digital maskless lithography quality by improved particle swarm optimization algorithm
Authors: Huang Shengzhou , Wu Dongjie , Tang Yuanzhuo , Ren Bowen , Pan Jiani , Tian Zhaowei , Li Zhi , Huang Jinjin
Published: September 2024

In this paper, an efficient mask optimization method for enhanced digital micromirror device lithography quality based on improved particle swarm optimization (PSO) is proposed, which greatly improves the quality of lithography. First, the traditional PSO algorithm is improved by introducing adaptive parameter adjustment to enhance its search ability in complex problems. In addition, in order to avoid premature convergence of the algorithm, a simulated annealing operation is introduced to make it accept the different solution with a certain probability and jump out of the local optimal better. The numerical simulation experiment results showed that the pattern errors between the print image and target pattern were reduced by 93.5%, 95.8%, and 95.6%, respectively. Compared with traditional optimization methods, the proposed algorithm significantly improves the image quality, especially in the aspects of edge contour and pattern fidelity.
A decarbonylative approach to alkylnickel intermediates and C(sp
3
)-C(sp
3
) bond formation
Authors: Huang Zhidao , Akana Michelle E. , Sanders Kyana M. , Weix Daniel J.
Published: September 2024

The myriad nickel-catalyzed cross-coupling reactions rely on the formation of an organonickel intermediate, but limitations in forming monoalkylnickel species have limited options for C(sp
3
) cross-coupling. The formation of monoalkylnickel(II) species from abundant carboxylic acid esters would be valuable, but carboxylic acid derivatives are primarily decarboxylated to form alkyl radicals that lack the correct reactivity. In this work, we disclose a facile oxidative addition and decarbonylation sequence that forms monoalkylnickel(II) intermediates through a nonradical process. The key ligand, bis(4-methylpyrazole)pyridine, accelerates decarbonylation, stabilizes the alkylnickel(II) intermediate, and destabilizes off-cycle nickel(0) carbonyl species. The utility of this new reactivity in C(sp
3
)-C(sp
3
) bond formation is demonstrated in a reaction that is challenging by purely radical methods—the selective cross-coupling of primary carboxylic acid esters with primary alkyl iodides.
Radical-mediated click-clip reactions
Authors: Zhao Jiantao , Yu Huacheng , Jin Xingchen , Qin Bo , Mei Shan , Xu Jiang-Fei , Zhang Xi
Published: September 2024

Click reactions, which are characterized by rapid, high-yielding, and highly selective coupling of two reaction partners, are powerful tools in synthesis but are rarely reversible. Innovative strategies that reverse such couplings in a precise and on-demand manner, enabling a click-clip sequence, would greatly expand the technique’s versatility. Herein, a click and clip reaction pair is demonstrated by manipulation of a sulfilimine linkage. Phenothiazines and amines are rapidly and quantitatively coupled through oxidative sulfilimine bond formation with N-bromosuccinimide, and the resulting sulfilimine bromides then undergo quantitative reversion to the phenothiazines and amines through photoreduction at 380 nanometers. This protocol enables fabrication of depolymerizable macromolecules and reversible modification of aminosaccharides, demonstrating high selectivity and efficiency for manipulating sulfilimine linkages in complex systems.
Atmospheric blocking slows ocean-driven melting of Greenland’s largest glacier tongue
Authors: McPherson Rebecca Adam , Wekerle Claudia , Kanzow Torsten , Ionita Monica , Heukamp Finn Ole , Zeising Ole , Humbert Angelika
Published: September 2024

Mass loss from the Greenland ice sheet has contributed to global sea-level rise over the past 20 years. Yet direct observations from the 79 North Glacier (79NG) calving front reveal decreasing Atlantic Intermediate Water (AIW) temperatures below the ice tongue from 2018 to 2021, leading to reduced ocean heat transport. This is linked to a concurrent decrease in basal melt and thinning rates at the grounding line. The origin of this AIW cooling is traced to a slowdown of the large-scale ocean circulation in the Nordic Seas, driven by European atmospheric blocking that strengthens cold air advection from the central Arctic through the Fram Strait. Blocking has driven major ocean cooling events over the last 50 years and will remain crucial in affecting Northeast Greenland’s glaciers.
The complex affective and cognitive capacities of rats
Authors: Ben-Ami Bartal Inbal
Published: September 2024

For several decades, although studies of rat physiology and behavior have abounded, research on rat emotions has been limited in scope to fear, anxiety, and pain. Converging evidence for the capacity of many species to share others’ affective states has emerged, sparking interest in the empathic capacities of rats. Recent research has demonstrated that rats are a highly cooperative species and are motivated by others’ distress to prosocial actions, such as opening a door or pulling a chain to release trapped conspecifics. Studies of rat affect, cognition, and neural function provide compelling evidence that rats have some capacity to represent others’ needs, to instrumentally act to improve their well-being, and are thus capable of forms of targeted helping. Rats’ complex abilities raise the importance of integrating new measures of rat well-being into scientific research.
The rat’s tale
Stowaway: The Disreputable Exploits of the Rat
Joe Shute
Bloomsbury, 2024. 272 pp.
Authors: Lynteris Christos
Published: September 2024

A charming rodent romp misses some of the creature’s most interesting and unsettling history
Ice skater
Authors: Andrews Robin George
Published: September 2024

Beneath Europa’s icy crust is a salty ocean, perhaps the best place in the Solar System to look for life. A NASA spacecraft will soon set off to probe the jovian moon
U.S. agency drops controversial changes to misconduct rules
Authors: Mervis Jeffrey
Published: September 2024

In first regulatory overhaul in 20 years, Office of Research Integrity takes modest steps toward greater transparency
Oxazolidinone antibiotics impair
ex vivo
megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets
Authors: Milosevic Tamara V. , Vertenoeil Gaëlle , Vainchenker William , Tulkens Paul M. , Constantinescu Stefan N. , Van Bambeke Françoise
Published: September 2024

Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes
ex vivo
and alter, in parallel, the activity of mitochondrial cytochrome
c
-oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.
What makes
Candida auris
pan-drug resistant? Integrative insights from genomic, transcriptomic, and phenomic analysis of clinical strains resistant to all four major classes of antifungal drugs
Authors: Rhodes Johanna , Jacobs Jonathan , Dennis Emily K. , Manjari Swati R. , Banavali Nilesh K. , Marlow Robert , Rokebul Mohammed Anower , Chaturvedi Sudha , Chaturvedi Vishnu
Published: September 2024

The global epidemic of drug-resistant
Candida auris
continues unabated. The initial report on pan-drug resistant (PDR)
C. auris
strains in a hospitalized patient in New York was unprecedented. PDR
C. auris
showed both known and unique mutations in the prominent gene targets of azoles, amphotericin B, echinocandins, and flucytosine. However, the factors that allow
C. auris
to acquire pan-drug resistance are not known. Therefore, we conducted a genomic, transcriptomic, and phenomic analysis to better understand PDR
C. auris
. Among 1,570 genetic variants in drug-resistant
C. auris
, 299 were unique to PDR strains. The whole-genome sequencing results suggested perturbations in genes associated with nucleotide biosynthesis, mRNA processing, and nuclear export of mRNA. Whole transcriptome sequencing of PDR
C. auris
revealed two genes to be significantly differentially expressed—a DNA repair protein and DNA replication-dependent chromatin assembly factor 1. Of 59 novel transcripts, 12 transcripts had no known homology. We observed no fitness defects among multi-drug resistant (MDR) and PDR
C. auris
strains grown in nutrient-deficient or -enriched media at different temperatures. Phenotypic profiling revealed wider adaptability to nitrogenous nutrients and increased utilization of substrates critical in upper glycolysis and tricarboxylic acid cycle. Structural modeling of a 33-amino acid deletion in the gene for uracil phosphoribosyl transferase suggested an alternate route in
C. auris
to generate uracil monophosphate that does not accommodate 5-fluorouracil as a substrate. Overall, we find evidence of metabolic adaptations in MDR and PDR
C. auris
in response to antifungal drug lethality without deleterious fitness costs.
A cynomolgus monkey
E. coli
urinary tract infection model confirms efficacy of new FimH vaccine candidates
Authors: Chorro Laurent , Ciolino Tara , Torres Caresse Lynn , Illenberger Arthur , Aglione JohnPaul , Corts Paula , Lypowy Jacqueline , Ponce Christopher , La Porte Annalena , Burt Deborah , Volberg Gretchen L. , Ramaiah Lila , McGovern Kathryn , Hu Jianfang , Anderson Annaliesa S. , Silmon de Monerri Natalie C. , Kanevsky Isis , Donald Robert G. K.
Published: September 2024

The increase in urinary tract infections (UTI) caused by antibiotic-resistant
Escherichia coli
requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR)
E. coli
serotype O25b ST131 isolate.
E. coli
fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively. Accordingly, we assessed the protective efficacy of three 50-µg intramuscular doses of a novel recombinant FimH antigen adjuvanted with liposomal QS21/MPLA compared with saline placebo in groups of nine animals. A third group was vaccinated with this FimH formulation in combination with 1 µg each of a four-valent mixture of serotype O1a, O2, O6, and O25b O-antigen CRM
197
lattice glycoconjugates. Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination group, O-antigen-specific antibodies. Following bacterial challenge, both vaccinated groups showed >200- and >700-fold reduction in bacteriuria at day 2 and day 7 post-infection compared with placebo, respectively. In parallel, both vaccines significantly reduced levels of inflammatory biomarkers IL-8 and myeloperoxidase in the urine at day 2 post-infection relative to placebo. Results provide preclinical proof-of-concept for the prevention of an MDR UTI infection by these new vaccine formulations.
Diagnostic performance of an automated robot for MALDI target preparation in microbial identification
Authors: Pranada Arthur B. , Cicatka Michal , Heß Clara , Karasek Jan
Published: September 2024

The MBT Pathfinder is an automated colony-picking robot designed for efficient sample preparation in matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. This article presents results from three key experiments evaluating the instrument’s performance in conjunction with MALDI Biotyper instrument. The method comparison experiment assessed its clinical performance, demonstrating comparable results with gram-positive, gram-negative, and anaerobic bacteria (scores larger than 2.00) and superior performance over simple direct yeast transfer (score: 1.80) when compared to samples prepared manually. The repeatability experiment confirmed consistent performance over multiple days and labs (average log score: 2.12, std. deviation: 0.59). The challenge panel experiment showcased its consistent and accurate performance across various samples and settings, yielding average scores between 1.76 and 2.19. These findings underline the MBT Pathfinder as a reliable and efficient tool for MALDI-TOF mass spectrometry sample preparation in clinical and research applications.
Complete genome sequence of cephalosporin and tetracycline-resistant
Citrobacter freundii
CF51 isolate from a patient with urinary tract infection
Authors: Sung Kidon , Nawaz Mohamed , Revollo Javier , Miranda Jaime A. , Feye Kristina , Park Miseon , Khan Saeed A.
Published: September 2024

We report here the complete genome sequence of cephalosporin (cefazolin and cephalotin) and tetracycline-resistant
Citrobacter freundii
strain CF51, isolated from a patient with a urinary tract infection. The genome comprises a 5.0-Mb chromosome, along with an 87.2-kb plasmid and a 23.9-kb plasmid.
Nine
Rhizobium
phage genomes recovered from wastewater in Tempe, AZ, October 2019–March 2020
Authors: Bermudez-Rivera Brenda , Hampton Brooklyn , Wheeler Cian , Vargas Jacqueline , Swaminathan Srivatsan , Driver Erin M. , Halden Rolf U. , Varsani Arvind , Scotch Matthew , Faleye Temitope O. C.
Published: September 2024

We describe nine
Rhizobium
microvirus genomes identified in wastewater in Tempe, AZ, USA, between October 2019 and March 2020. The major capsid protein (MCP) encoded in these genomes phylogenetically cluster together and are distinct from the MCPs of
Rhizobium
microviruses identified in Mexico and Argentina.
The gut microbiota as an early predictor of COVID-19 severity
Authors: Fabbrini Marco , D’Amico Federica , van der Gun Bernardina T. F. , Barone Monica , Conti Gabriele , Roggiani Sara , Wold Karin I. , Vincenti-Gonzalez María F. , de Boer Gerolf C. , Veloo Alida C. M. , van der Meer Margriet , Righi Elda , Gentilotti Elisa , Górska Anna , Mazzaferri Fulvia , Lambertenghi Lorenza , Mirandola Massimo , Mongardi Maria , Tacconelli Evelina , Turroni Silvia , Brigidi Patrizia , Tami Adriana
Published: September 2024

Several studies reported alterations of the human gut microbiota (GM) during COVID-19. To evaluate the potential role of the GM as an early predictor of COVID-19 at disease onset, we analyzed gut microbial samples of 315 COVID-19 patients that differed in disease severity. We observed significant variations in microbial diversity and composition associated with increasing disease severity, as the reduction of short-chain fatty acid producers such as
Faecalibacterium
and
Ruminococcus
, and the growth of pathobionts as
Anaerococcus
and
Campylobacter
. Notably, we developed a multi-class machine-learning classifier, specifically a convolutional neural network, which achieved an 81.5% accuracy rate in predicting COVID-19 severity based on GM composition at disease onset. This achievement highlights its potential as a valuable early biomarker during the first week of infection. These findings offer promising insights into the intricate relationship between GM and COVID-19, providing a potential tool for optimizing patient triage and streamlining healthcare during the pandemic.

IMPORTANCE

Efficient patient triage for COVID-19 is vital to manage healthcare resources effectively. This study underscores the potential of gut microbiota (GM) composition as an early biomarker for COVID-19 severity. By analyzing GM samples from 315 patients, significant correlations between microbial diversity and disease severity were observed. Notably, a convolutional neural network classifier was developed, achieving an 81.5% accuracy in predicting disease severity based on GM composition at disease onset. These findings suggest that GM profiling could enhance early triage processes, offering a novel approach to optimizing patient management during the pandemic.
Continental rift evolution and drainage reorganization along the Dead Sea rift since the Miocene
Authors: Matmon A. , Avni Y. , Guralnik B. , Hidy A.
Published: September 2024

The Dead Sea fault is a section of the Arabian-African plate boundary. Widespread field relations indicate that three major drainage systems (stages) occupied the landscape west of the Dead Sea fault since its initiation at ca. 20 Ma. Specifically, (1) an early to middle Miocene drainage system, only minorly reconfigured by the fault (all sediments of this system belong to the Hazeva Formation); (2) a late Miocene to early Pleistocene fault-parallel drainage system named Paran-Neqarot (all sediments of this system belong to the Arava and Zehiha Formations; and (3) the early Pleistocene to present drainage configuration. The temporal and spatial frameworks of drainage stage 1 are generally constrained by radiometric dating of interfingering volcanic units, and the onset and temporal and spatial frameworks of drainage stage 3 are well constrained by cosmogenic 10Be surface exposure ages. The timing and longevity of the rift-parallel drainage (stage 2) have until now been evasive to direct dating. The overall time gap between stages 1 and 3 is ~12–13 million years. Thus, an early age (within this time gap) of stage 2 would imply an immediate response of drainage reorganization to rift tectonics, while a later age of this drainage system would imply a delayed response. We present 11 10Be-26Al cosmogenic burial ages of alluvial and colluvial units related to the fault-parallel drainage system (stage 2), which collectively constrain the time of deposition of the Arava Formation sediments in the central Negev to ca. 8 Ma. The general lack of stratigraphic order, together with the large dispersion of ages both across and within the sampling sites, attests to significant recycling of sediments from drainage stage 1 into the Arava Formation deposits. The termination of Arava and Zehiha Formation sediment deposition at ca. 1.8 Ma was determined previously using cosmogenic exposure ages of desert pavements that cover the formations. Combining the previously published data with our new data, we established the longevity and character of the Paran-Neqarot drainage system. This framework highlights the temporal aspect of drainage system build-up and collapse as it responded to transform and extensional plate boundary tectonics during the Neogene.