bluuebunny/crossref_metadata_2025 huggingface dataset:
Review on Antagonists
Authors: Sardana Divya
Published: April 2015

Gonadotropin-releasing hormone (GnRH) antagonists have been a breakthrough in reproductive medicine. The third generation antagonists (cetrorelix and ganirelix) do not have histamine releasing capability in the used doses. The competitive blockade of GnRH receptors by GnRH antagonists leads to an immediate but reversible arrest of gonadotropin secretion. Antagonists can be used as single-dose or multiple dose protocol in a fixed or flexible approach during ovarian stimulation to prevent premature luteinizing hormone surge. The stimulation remains close to the normal cycle, and more convenient and friendly to the patient with lesser dose and duration of stimulation. Recent Cochrane analysis suggests that there is no significant difference in the live birth rate when antagonists are compared with agonists (OR 0.86) and there is a significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) (OR 0.43) with the use of antagonists. Gonadotropin-releasing hormone antagonists are of special benefit for use in patients with polycystic ovaries where agonist trigger can be used and OHSS can be prevented completely. Gonadotropin-releasing hormone antagonists have particular advantage in poor responders with lesser pituitary suppression in the early part of cycle. Gonadotropinreleasing hormone antagonists can be used in modified natural cycle, intrauterine insemination cycles, and frozen embryo transfer cycles. Novel uses of antagonists include suppression of established OHSS, and in various gynecological conditions (endometriosis, fibroids, precocious puberty).

How to cite this article

Sardana D. Review on Antagonists. Int J Infertil Fetal Med 2015;6(1):1-10.
Combined Tamoxifen and L-Carnitine Therapies for the Treatment of Idiopathic Male Infertility Attending Intracytoplasmic Sperm Injection: A Randomized Controlled Trial
Authors: Haje Milat , Naoom Kameel
Published: April 2015

Aim

The aim of the present study is to evaluate the fertility outcomes of intracytoplasmic sperm injection (ICSI) as well as sperm count, motility and morphology in couples with infertile male partners exhibiting idiopathic oligoasthenozoospermia (OA) and treated with tamoxifen citrate and/or L-carnitine.

Materials and methods

In this randomized controlled trail, couples with female cause of infertility were excluded. Only couples with male cause of infertility with idiopathic OA were admitted to this study and randomly assigned into four different groups of treatments as follow: Group A (n = 45) received an anti-estrogen compound (tamoxifen 20 mg/day), group B (n = 20) received L-carnitine (1000 mg/day), group C (n = 34) received tamoxifen 20 mg/day plus L-carnitine 1000 mg/day, whereas group D (n = 29) received placebo. Treatments were continued for 3 to 6 months.

Results

Treatment groups of A, B, and C showed an overall improvement in the tested parameters of sperm when compared to the control group that showed an overall reduction in those parameters after termination of the treatment. In this context, sperm count increased from 7.58 ± 2.93 × 106/ml before treatment to 10.81 ± 1.84 × 106/ml after treatment in group A (p = 0.016). Similarly, sperm count increased from 5.32 ± 2.09 × 106/ml to 8.92 ± 2.29 × 106/ml in group C (p = 0.01). Patients from group C did not only have an improved total motility of sperm from 8.03 ± 1.59% to 13.78 ± 3.85% (p = 0.045) but also an improved sperm normal morphology from 0.88 ± 0.45% to 1.99 ± 0.71% (p = 0.026). Patients from group A or C exhibited an improved ICSI outcomes when compared to those in patients from group B or D (48.9 or 48.3 vs 16.6 or 20, respectively, p = 0.46).

Conclusion

It is concluded that administration of tamoxifen and L-carnitine can improve both sperm parameters of fertility and ICSI outcomes. Combined tamoxifen and L-carnitine treatments result in maximum therapeutic effect in men with idiopathic OA.

How to cite this article

Haje M, Naoom K. Combined Tamoxifen and L-Carnitine Therapies for the Treatment of Idiopathic Male Infertility Attending Intracytoplasmic Sperm Injection: A Randomized Controlled Trial. Int J Infertil Fetal Med 2015;6(1):20-24.
The History of British Literature on Film, 1895–2015
Authors: Colón Semenza Greg M. , Hasenfratz Bob
Published: April 2015

From The Death of Nancy Sykes (1897) to The Hobbit: The Battle of the Five Armies (2014) and beyond, cinematic adaptations of British literature participate in a complex and fascinating history. The History of BritishLiterature on Film, 1895-2015 is the only comprehensive narration of cinema's 100-year-old love affair with British literature. Unlike previous studies of literature and film, which tend to privilege particular authors such as Shakespeare and Jane Austen, or particular texts such as Frankenstein, or particular literary periods such as Medieval, this volume considers the multiple functions of filmed British literature as a cinematic subject in its own right—one reflecting the specific political and aesthetic priorities of different national and historical cinemas. In what ways has the British literary canon authorized and influenced the history and aesthetics of film, and in what ways has filmed British literature both affirmed and challenged the very idea of literary canonicity? Seeking to answer these and other key questions, this indispensable study shows how these adaptations emerged from and continue to shape the social, artistic, and commercial aspects of film history.
Tetra-primer ARMS-PCR identified a missense mutation of the bovine NRIP1 gene associated with growth traits
Authors: Liu D. , Wang Z. , Ma W. , Gao Y. , Li A. , Lan X. , Lei C. , Chen H.
Published: April 2015

Abstract. Nuclear receptor-interacting protein 1 (NRIP1) specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors to inhibit transcription. Previous work has demonstrated this protein to be a key regulator in modulating transcriptional activity of many transcription factors, some of which are closely related to development and growth. In this study, we have successfully genotyped two newly identified bovine NRIP1 single-nucleotide polymorphisms (SNPs) (c.605A > G and c.1301G > A) using the T-ARMS-PCR method and validated the accuracy by means of PCR-RFLP assay using 1809 individuals of 9 different cattle breeds. The association analyses results indicated that c.605A > G locus was significantly associated with body weight and average daily gain in Nanyang cattle at 18 months (P < 0.05). Thus it can be inferred that T-ARMS-PCR is a rapid, reliable, and cheap method for SNP genotyping and that c.605A > G polymorphism in bovine NRIP1 is associated with growth traits. These findings will be of benefit for the application of DNA markers related to growth traits in marker-assisted selection (MAS), and will improve the promotion of beef cattle.
THERMOREVERSIBLE COVALENT CROSS-LINKING OF MALEIC ANHYDRIDE GRAFTED BUTYL RUBBER WITH GLYCEROL
Authors: Li Lin , Zhao Shuai , Ma Zhenguo , Xin Zhenxiang
Published: April 2015

The formation of thermoreversible hemi-ester cross-links of maleic anhydride grafted butyl rubber (MAn-g-IIR) using glycerol as a cross-linking agent in the absence of catalyst was studied in the present work. The effects of the molar ratios of glycerol to anhydride, the amount of the mixed solvent, the reaction temperature, and the reaction time on the percentage conversion of anhydride to ester were determined. The maximum percentage conversion calculated from the Fourier transform infrared spectroscopy spectra was 52.11. Reaction temperature played the most important role on the percentage conversion, followed by reaction time. Compared with the original MAn-g-IIR, tensile strength of the hemi-ester cross-linked MAn-g-IIR was significantly improved. These macromolecular regular clusters acted as strong and multiple cross-linking points that led to impressive mechanical properties. This confirmed the formation of hemi-ester cross-links. The covalently cross-linked MAn-g-IIR was reprocessable via compression molding at 179 °C and higher, indicating that the cross-links were indeed thermoreversible. The cross-linked materials could be repeatedly compression molded at 179 °C into homogeneous films for at least three cycles.
Cooperative Intrasectoral Specialization as A Regional Growth Strategy in Northeast Asia
Authors: Jung Walter B
Published: April 2015

No abstract available. DOI: http://dx.doi.org/10.5564/mjia.v4i0.418 Mongolian Journal of International Affairs Vol.4 2007: 35-47
PKM Mechatronic Clamping Adaptive Device
Authors: Borboni Alberto , Aggogeri Francesco , Merlo Angelo , Pellegrini Nicola , Amici Cinzia
Published: April 2015

This study proposes a novel adaptive fixturing device based on active clamping systems for smart micropositioning of thin-walled precision parts. The modular architecture and the structure flexibility make the system suitable for various industrial applications. The proposed device is realized as a Parallel Kinematic Machine (PKM), opportunely sensorized and controlled, able to perform automatic error-free workpiece clamping procedures, drastically reducing the overall fixturing set-up time. The paper describes the kinematics and dynamics of this mechatronic system. A first campaign of experimental trails has been carried out on the prototype, obtaining promising results.
The Perceived Impact of E-books on Student Reading Practices: A Local Study
Authors: Gilbert Julie , Fister Barbara
Published: April 2015

This study investigates the perceived impact of future e-book collections on student research and recreational reading habits at our institution through three questions: how students currently use library print collections, how students use e-books, and how these factors impact student perception of the effects of future library e-books on their research and recreational reading behavior. Students express a fairly high interest in e-books, although not without raising significant concerns. While students appreciate the ease of access provided by e-books, many imagine that research would be more difficult using e-books. Results will help the library better evaluate e-book options and navigate possible issues related to implementation.
Application of the Welfare Quality®animal welfare assessment system in Finnish pig production, part II: Associations between animal-based and environmental measures of welfare
Authors: Munsterhjelm C , Heinonen M , Valros A
Published: April 2015

This study aimed to establish associations between the environment and animal-based measures of welfare collected on 158 Finnish farms according to the Welfare Quality® systems for pigs. The data consisted of 95 welfare assessments in fattening pigs and 103 in sows, including suckling piglets. Principal Component Analysis had previously been applied to animal-based welfare measures (ABWM) and to the 20 descriptors of QBA to identify distinct types of welfare problems (WPT) and mood (MT), respectively. Generalised linear modeling was used to investigate environmental (space allowance, group size, feeding arrangement, floor type and use of enrichment or bedding) effects on WPT and MT scores. Those ABWMs not contributing to the major WPTs, but occurring on more than 40% of the farms, were considered important and used as outcome variables as well. The most important environmental determinants of pig welfare were space allowance for fattening pigs, group size in gestation and in the use of bedding for both fattening pigs and gestating sows. Bedding decreased tail biting and signs of fighting when used as a fairly thick layer for fattening pigs. In sows, the benefits of bedding, including less frustration and bursitis, required a smaller amount of material than in fattening pigs. An increasing space allowance was advantageous for fattening pigs, although signs of fighting increased in very spacious bedded pens. The positive effects of space, including a decrease of tail lesions and a more positive mood continued at least up to 1.5 m2per fattening pig. Signs of resource shortage in sows increased with a growing group size according to a steepening curve.
Effect of different management techniques to enhance colostrum intake on piglets’ growth and mortality
Authors: Muns R , Manteca X , Gasa J
Published: April 2015

An experiment was conducted to study the effect four different management techniques to enhance colostrum intake had on piglet and litter performance. Treatments were performed on piglets born weighing 1.30 kg or less (SP) within 6 h of birth: control group (CON); split-nursing of the litter for 2 h allowing only the SP piglets free access to teats (SPLIT); oral supplementation with 15 ml of sow colostrum to the SP piglets of the litter (COL); and oral supplementation with 3 ml of an energy product (Calostrene®) to the SP piglets of the litter (EN). Thirty-nine primiparous sows (Large White × Landrace) and their litters (507 piglets) and 100 multiparous sows and their litters (1,375 piglets) were used. Litters were fixed at 12 piglets. Piglets were weighed through lactation. Mortality was recorded. For primiparous sows, oral supplementation with COL enhanced SP piglets bodyweight (BW) at day 1 compared to CON, SPLIT, and EN. However, no differences on BW were observed at day 18 nor on litter total pre-weaning mortality. Nonetheless, lower SP piglets’ mortality rate was found in CON and EN compared to SPLIT and COL groups in primiparous sows. For multiparous sows, no differences among treatments were observed for SP piglets BW at day 1 or at day 18. Primiparous sows’ SP piglets had higher BW at day 1 than multiparous sows’ SP piglets. Colostrum supplementation of low birth weight piglets improved early weight gain in piglets born from primiparous sows, probably by enhancing their colostrum intake, but it did not affect piglets’ weaning BW or pre-weaning mortality.
Préserver la durabilité des pratiques informationnelles des acteurs de l’architecture éco-constructive : des pratiques informationnelles à une mémoire collective de travail
Authors: Liquète Vincent
Published: April 2015

L’objectif de cette contribution sera de poser les prémisses d’une organisation de la durabilité des pratiques informationnelles en contexte professionnel. Nous tenterons de dégager quelques éléments clefs à prendre en considération pour concevoir l’accompagnement de la durabilité des pratiques informationnelles en contexte professionnel. Pour ce faire, cette contribution croisera un travail d’analyse d’un corpus sur la question fondamentale de la durabilité, avec un ensemble d’éléments que nous avons recueillis lors d’entretiens et d’analyses des systèmes d’information chez les architectes aquitains spécialisés en éco-construction. En effet, les acteurs aquitains du secteur de l’architecture éco-constructive (architectes, ingénieurs, fournisseurs, constructeurs, etc.), bien qu’ayant des pratiques informationnelles affirmées, organisent et conservent l’information de manière encore rare, sporadique, parfois même hasardeuse et fragmentée. Nous serons alors amenés à suggérer dans cette double approche pragmatique et théorique, un schéma de durabilité pour faciliter l’émergence puis le maintien de pratiques informationnelles durables. La question notamment de la constitution d’une mémoire numérique de travail, inscrivant leurs pratiques informationnelles autour des principes de durabilité, de stabilité et de transférabilité, sera évoquée.
La veille : un élément structurant de la construction d’une professionnalité pour les étudiants en master documentation ?
Authors: Thiault Florence , Kerneis Jacques , Rouillard Rozenn , Peirano Richard
Published: April 2015

Notre recherche propose une réflexion sur les pratiques de veille informationnelle d’étudiants qui préparent un master documentation en France, afin de devenir professeur-documentaliste. Parallèlement, cette étude vise à mieux connaître les étudiants qui suivent cette formation et leurs besoins. Les données émanent d’une enquête quantitative et qualitative menée dans le cadre singulier d’un dispositif d’ingénierie coopérative qui vise à articuler recherche et formation. Les principaux résultats soulignent que les étudiants n’ont pas nécessairement d’usages professionnels numériques développés et que l'installation de pratiques info-communicationnelles durables chez les étudiants seraient de nature à développer leur professionnalité.
Les enjeux et les défis du développement territorial durable dans une région à problèmes : le cas du comté de Restigouche au Nouveau-Brunswick
Authors: Laplante Pierre , Simard Majella
Published: April 2015

Cet article s’inscrit dans la foulée d’une problématique récurrente en développement régional : celle des disparités. En raison de sa vaste étendue et de la faiblesse de sa population, le Canada se distingue par la persistance de disparités qui ont tendance à se manifester avec une plus grande acuité dans les régions situées à l’est du pays. Le Restigouche s’inscrit dans cette perspective. Située au nord du Nouveau-Brunswick, cette région se caractérise par la persistance de nombreuses disparités socio-économiques par rapport à la province. De fait, celle-ci est aux prises avec un sous-emploi chronique, de faibles niveaux de revenus, une dépendance à l’égard des transferts gouvernementaux, un affaiblissement de son infrastructure de services ainsi qu’avec le dépeuplement de son territoire. En outre, la crise du bois d’oeuvre a affecté l’économie de cette région tributaire de l’exploitation de la forêt. Comment les acteurs du Restigouche perçoivent-ils la situation socio-économique de leur milieu ? Telle est la principale question qui sert de fil conducteur à cet article dont l’objectif consiste à analyser, sous l’angle des représentations sociales, les enjeux et les défis du développement territorial durable dans le comté de Restigouche. Notre cadrage conceptuel s’appuie sur les notions de développement territorial durable et de représentations sociales. Au plan méthodologique, la démonstration des résultats est effectuée à partir des données de Statistique Canada et d’enquêtes sur le terrain. Ceux-ci révèlent une accentuation des disparités socio-économiques entre 1986 et 2006. Bien que leur appréciation diffère selon les acteurs locaux, ces derniers admettent que leur persistance est difficilement conciliable avec un développement territorial durable et que leur résorption relève de l’État.
The Dream of Large-Scale Truck Transport Enterprises — Outsourcing Experiments in the German Democratic Republic, 1957–80
Authors: Vahrenkamp Richard
Published: April 2015

Under state socialist economic policy, the concept of large-scale factories played an important role. The assumption was that large productivity gains would result from large-scale organisation and so large-scale concepts were also applied to the transport sector. Thirty years before Western management started outsourcing truck transportation from their factories, from 1957 state socialist traffic policy in the German Democratic Republic pulled truck fleets out of nationally owned enterprises, concentrating them into large and dedicated transport service enterprises. As this policy did not increase productivity, it was partly revised in the 1960s. The centralisation policy was unsuccessful because state-owned enterprises struggled against the state socialist transport department to keep the fleets they needed to conduct business. Conflicts between the state socialist ideology of centralisation and the operational needs of transportation within commerce, construction and industry took on many forms. For example the enterprises transferred only old trucks to the service companies. The paper shows that the theorem of the ‘economies of scale’ that was derived in the process industries does not apply in the transportation trade.
Charabancs and Social Class in 1930s Britain
Authors: Law Michael John
Published: April 2015

The renowned writer J. B. Priestley suggested in 1934 that the motor-coach had annihilated the old distinction between rich and poor passengers in Britain. This article considers how true this was by examining the relationship between charabancs, motor coaches and class. It shows that this important vehicle of inter-war working class mobility had a complicated relationship with class, identifying three distinct forms of this method of travel. It positions the charabanc alongside historical responses to unwelcome steamer and railway day-trippers, and examines how resorts provided separate class-based entertainment for these holidaymakers. Using the case study of a new charabanc-welcoming pub, the Prospect Inn, it proposes that, in the late 1930s, some pubs were beginning to offer charabanc customers facilities that were almost the match of their middle class equivalent. Motor coaches and charabancs contributed to the process of social convergence in inter-war Britain.
An integrated methodology to define Protection Zones for groundwaterbased drinking water sources: an example from the Tuscany Region, Italy
Authors: Menichini Matia , Da Prato Simone , Doveri Marco , Ellero Alessandro , Lelli Matteo , Masetti Giulio , Nisi Barbara , Raco Brunella
Published: April 2015

Water is an essential economic and social resource. It is also finite and vulnerable. For Europe, this generally accepted understanding has been translated into the European and National Directive (2000/60/EC, D.Lgs. 152/2006). This law has led to an increased awareness of the role of the resource and its importance in the socioeconomic, cultural, and political realms. To protect this resource, safeguard zones for drinking water sources must be delineated. In Italy, a drinking water source such as a well or spring is to be protected by means of a three-level safeguard zone: an absolute safety zone close to the source, a respect zone depending on groundwater travel time, and a Protection Zone. The aim of this paper is to describe an integrated methodology used to define the Protection Zone. The work, developed within the framework of a project of the Institute of Geosciences and Earth Resources (IGG-CNR) and funded by the Tuscany Region Administration through “Consorzio Lamma”, focused on the delineation of the Protection Zones for several abstraction points located throughout the regional territory. The proposed methodology for protecting drinking water sources described in this paper integrates geological, hydrogeological, and hydrogeochemical methodologies. The approach includes a definition of the hydrostratigraphy of the aquifer systems, estimates of the water volume, and the quantification of inflows and outflows, as well their interrelationships. By means of this integrated methodology, fifteen Protection Zones were defined; each of these zones was divided in two areas according to their relative importance to supplying a drinking water source. The Protection Zones were further validated by means of hydrogeological and isotopic budget calculations.
MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture
Authors: Friedman Jonathan R , Mourier Arnaud , Yamada Justin , McCaffery J Michael , Nunnari Jodi
Published: April 2015

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of both MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.
Mechanism and development model of karsts in Ordovician buried hills in western Lungu area, Tarim Basin
Authors: Qingyu Zhang , Bin Liang , Jianwen Cao , Yong Dan , Yanzhen Hao , Jingrui Li
Published: April 2015

In the western Lungu area in the Tarim Basin, dissolution pores, holes and fractures served as reservoir space in the Ordovician carbonate rocks. The karst reservoirs had a strong heterogeneity, and were classified into four types, including fracture, hole, fracture - hole, and cave. In different landscape units, the karsted fracture and hole system was vertically zoned. The mechanism of karst was studied with sheet analysis, and a developmentmodel of the karst reservoir in the Ordovician western Lungu carbonate rocks was established. The Lungu7 block in the east was the highest in the study area, and recharged the buried hills in Lunnan. The karst platform in the western Lungu area recharged the western Lungu area. Meteoric water infiltrated, forming dissolution pores and fractures, which were filled by clays and calcites. On the karst slope, groundwater migrated horizontally, and a karst river/pipeline system developed, filled by karst breccias and clays. The karst basin drainage area determined the scale of karst development.
Expanded Child Tax Credit and Food Insecurity
Authors: Berkowitz Seth A. , Palakshappa Deepak
Published: August 2024

This cohort study examines changes in food security associated with the 2021 Expanded Child Tax Credit enactment and expiration in 2 individual-level, longitudinal, nationally representative cohorts.
Clinician Specialty and HIV PrEP Prescription Reversals and Abandonments
Authors: Bakre Shivani , Chang Hsien-Yen , Doshi Jalpa A. , Goedel William C. , Saberi Parya , Chan Philip A. , Nunn Amy , Dean Lorraine T.
Published: August 2024

Importance

Clinicians are a key component of preexposure prophylaxis (PrEP) care. Yet, no prior studies have quantitatively investigated how PrEP adherence differs by clinician specialty.

Objective

To understand the association between prescribing clinician specialty and patients not picking up (reversal/abandonment) their initial PrEP prescription.

Design, Setting, and Participants

This cross-sectional study of patients who were 18 years or older used pharmacy claims data from 2015 to 2019 on new insurer-approved PrEP prescriptions that were matched with clinician data from the US National Plan and Provider Enumeration System. Data were analyzed from January to May 2022.

Main Outcomes and Measures

Clinician specialties included primary care practitioners (PCPs), infectious disease (ID), or other specialties. Reversal was defined as a patient not picking up their insurer-approved initial PrEP prescription. Abandonment was defined as a patient who reversed and still did not pick their prescription within 365 days.

Results

Of the 37 003 patients, 4439 (12%) were female and 32 564 (88%) were male, and 77% were aged 25 to 54 years. A total of 24 604 (67%) received prescriptions from PCPs, 3571 (10%) from ID specialists, and 8828 (24%) from other specialty clinicians. The prevalence of reversals for patients of PCPs, ID specialists, and other specialty clinicians was 18%, 18%, and 25%, respectively, and for abandonments was 12%, 12%, and 20%, respectively. After adjusting for confounding, logistic regression models showed that, compared with patients who were prescribed PrEP by a PCP, patients prescribed PrEP by ID specialists had 10% lower odds of reversals (odds ratio [OR], 0.90; 95% CI, 0.81-0.99) and 12% lower odds of abandonment (OR, 0.88; 95% CI, 0.78-0.98), while patients prescribed by other clinicians had 33% higher odds of reversals (OR, 1.33; 95% CI, 1.25-1.41) and 54% higher odds of abandonment (OR, 1.54; 95% CI, 1.44-1.65).

Conclusion

The results of this cross-sectional study suggest that PCPs do most of the new PrEP prescribing and are a critical entry point for patients. PrEP adherence differs by clinician specialties, likely due to the populations served by them. Future studies to test interventions that provide adherence support and education are needed.
GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain
Authors: Guo Xiaohui , Zhang Tingting , Yuan Geheng , Zeng Weifang , Hu Qingyuan , Ma Jianhua , Li Yukun , Li Hongmei , Zhang Yawei , Liu Jie , Bian Fang , Zhang Wei , Zhang Fang , Pang Shuguang , Li Ya , Wu Xiaohong , Tang Xulei , Zhang Keqin , Pan Tianrong , Hu Honglin , Cheng Zhifeng , Wang Yanjun , Gao Jialin , Sun Jia
Published: August 2024

Importance

Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China.

Objective

To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP.

Design, Setting, and Participants

This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose.

Intervention

In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment.

Main Outcomes and Measures

The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences.

Results

Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was −2.24 (1.55) for the 40-mg/d and −2.16 (1.79) for 80-mg/d groups and −1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.

Conclusions and Relevance

Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated.

Trial Registration

ClinicalTrials.gov Identifier: NCT04647773
Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Wessels Lars , Wolf Stefan , Adage Tiziana , Breitenbach Jörg , Thomé Claudius , Kerschbaumer Johannes , Bendszus Martin , Gmeiner Matthias , Gruber Andreas , Mielke Dorothee , Rohde Veit , Wostrack Maria , Meyer Bernard , Gempt Jens , Bavinzski Gerhard , Hirschmann Dorian , Vajkoczy Peter , Hecht Nils
Published: August 2024

Importance

Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.

Objective

To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.

Design, Setting, and Participants

This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated.

Intervention

During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group).

Main Outcome and Measures

The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography.

Results

Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups.

Conclusions and Relevance

These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted.

Trial Registration

ClinicalTrials.gov Identifier: NCT04269408
Metabolic dysregulation‐triggered neutrophil extracellular traps exacerbate acute liver failure
Authors: Zhang Kangnan , Jia Rongrong , Zhang Qinghui , Xiang Shihao , Wang Na , Xu Ling
Published: August 2024

Acute liver failure (ALF) is an acute liver disease with a high mortality rate in clinical practice, characterized histologically by extensive hepatocellular necrosis and massive neutrophil infiltration. However, the role of these abnormally infiltrating neutrophils during ALF development is unclear. Here, in an ALF mouse model, metabolites were identified that promote the formation of neutrophil extracellular traps (NETs) in the liver, subsequently influencing macrophage differentiation and disease progression. ALF occurs with abnormalities in hepatic and intestinal metabolites. Abnormal metabolites (LTD4 and glutathione) can directly, or indirectly via reactive oxygen species, promote NET formation of infiltrating neutrophils, which subsequently regulate macrophages in a pro‐inflammatory M1‐like state, inducing an amplification of the destructive effects of inflammation. Together, this study provides new insights into the role of NETs in the pathogenesis of ALF.
A Microstructure‐Enhanced Dual‐Mode LC Sensor with a PSO‐BP Algorithm for Precise Detection of Temperature and Pressure
Authors: Miao Hailiang , Bi Jinglong , Gao Yang , Wang Yiming , Wang Tao , Mo Runwei , Qian Min , Zhu Mingliang , Xuan Fuzhen
Published: August 2024

High‐sensitivity flexible wireless passive sensors with multiple parameters sensing capability are highly demanded for industrial production, structural health monitoring, and medical care. In this study, a microstructure‐enhanced temperature and pressure dual‐mode inductance capacitance (LC) sensor is developed with a particle swarm optimization‐back propagation (PSO‐BP) algorithm for simultaneous measurement of temperature and pressure. In the device, two interdigital electrodes connected at different parts of an inductor is used to realize dual‐mode measurement of pressure and temperature, with reduced volume and cost of the device as well as avoided interaction of the superimposed inductance. The sandpaper‐molded polydimethylsiloxane microstructures are employed to enhance the device sensitivity, with six and three times of improvement in temperature and pressure sensitivity, respectively. A PSO‐BP neural network suitable for regression analysis of low dimensional small sample data is constructed to achieve the simultaneous measurement of pressure and temperature with an accuracy up to 94%. Furthermore, investigations have proved the promising applications of the dual‐mode LC sensor in health monitoring of lithium‐ion batteries and detection of plantar pressure for medical care.
Ferroelectricity‐Tuned Band Topology and Superconductivity in 2D Materials and Related Heterostructures
Authors: Chen Jianyong , Cui Ping , Zhang Zhenyu
Published: August 2024

Ferroelectricity, band topology, and superconductivity are respectively local, global, and macroscopic properties of quantum materials, and understanding their mutual couplings offers unique opportunities for exploring rich physics and enhanced functionalities. In this mini‐review, the attempt is to highlight some of the latest advances in this vibrant area, focusing in particular on ferroelectricity‐tuned superconductivity and band topology in 2D materials and related heterostructures. First, results from predictive studies of the delicate couplings between ferroelectricity and topology or superconductivity based on first‐principles calculations and phenomenological modeling are presented, with ferroelectricity‐enabled topological superconductivity as an appealing objective. Next, the latest advances on experimental studies of ferroelectricity‐tuned superconductivity based on different 2D materials or van der Waals heterostructures are covered. Finally, as perspectives, schemes are outlined that may allow to materialize new types of 2D systems that simultaneously harbor ferroelectricity and superconductivity, or that may lead to enhanced ferroelectric superconductivity, ferroelectric topological superconductivity, and new types of superconducting devices such as superconducting diodes.
Advanced Stretchable Aerogels and Foams for Flexible Electronics and Beyond
Authors: Liang Xing , Sun Qi , Zhang Xiaoyu , Hu Zhenyu , Liu Muxiang , Gu Puzhong , Yang Xiao , Zu Guoqing
Published: August 2024

With the increasing demands for artificial intelligence, robotics, electronic skin, healthcare, and energy storage/conversion, the research focus on flexible electronics has started to shift from being merely bendable and rollable to being stretchable. In recent years, stretchable aerogels and foams have drawn significant attention in the field of flexible electronics due to their unique porous structures, low density, high porosity, and high flexibility. This work provides a comprehensive review of the state‐of‐the‐art developments in stretchable aerogels and foams, encompassing their preparation, structures, properties, and applications. The preparation methods, typical structures of stretchable aerogels and foams, stretching principle, and the relationship between their structures, stretchability, and other properties are investigated. Their latest applications in stretchable strain/pressure sensors, electrodes and conductors, chemical sensors and biosensors, supercapacitors, batteries, triboelectric nanogenerators, electromagnetic shielding, microwave absorption, thermal management, adsorption, separation/filtration, and shape memory are introduced. Furthermore, the challenges and opportunities of stretchable aerogels and foams are summarized. This work provides a guideline for the development of stretchable aerogels and foams and next‐generation high‐performance flexible electronics based on stretchable porous materials.
Self‐Powered Luminescent Solar Concentrators‐Integrated Temperature Detection System with High Thermal Tolerance by Reversible Thermal Photoluminescence Luminophores
Authors: Guo Haotian , Xia Pengfei , Huang Shichao , Sun Hongcan , Lu Changgui , Liang Cai , Zhou Xiaoxi , Xu Shuhong , Wang Chunlei
Published: August 2024

It is still a challenge to prepare the red‐emissive perovskite‐polymer composite with high photoluminescence quantum yield (PLQY) and reversible thermal photoluminescence (RTPL), which is key for improving the thermal tolerance of luminescent solar concentrators (LSCs). In this work, the red‐emissive (661 nm) CsPb(Br0.25I0.75)3‐PMMA composite with high PLQY of 85.96% and favorable RTPL below 160 °C is reported via a strategy of the defect passivation by halide ligand additives. The composite film possesses excellent long‐term stability in air, water, and high temperature environments. Then, a self‐powered temperature detection system, which consists of LSCs and a temperature detection module based on the RTPL composite film, is fabricated. On one hand, RTPL composite makes LSCs of superior thermal tolerance even after 100 cycles of temperature between room temperature and 160 °C. On the other hand, RTPL composite in the opaque box of the temperature detection module can give rise to the signal light without the interference of ambient light. As a result, the self‐powered temperature detection system achieves the quantitative temperature data display at different environment lights for 24 h in a day.
Asymmetrical Promotional Effect in the Disorder‐to‐Order Transition of Au‐Pt‐Cu Ternary Alloy Electrocatalysts
Authors: Zhao Wenbo , Hu Zheng , Li Mengyao , Hu Shi
Published: August 2024

Binary alloys of platinum (Pt) are well‐studied to address the poor poisoning resistance of Pt. Among them, the ordered alloys, also known as intermetallics, tend to show exceptional advantages in activity and durability. In contrast, the medium and high‐entropy Pt alloy systems, with three or more elements, have been reported with better performance but not fully understood, due to the complex relationship of elemental miscibility. Herein a unique asymmetric synergistic effect in the ordering process of a series of ternary alloy AuxPt1‐xCu3 (x = 0‐1) is reported. The volcano plot of ordering degree (OD) in AuxPt1‐xCu3 (x = 0‐1) shows its peak in the Au‐rich samples but gradually shifts to Au/Pt equal molar ratio with the increasing temperature. Based on formation energy calculation and molecular dynamics analysis, the unique ordering trend of ternary alloys and the shift of OD peak position are rationalized. Among the studied samples, Au0.4Pt0.6Cu3‐350 sample exhibits the highest mass activity in electrocatalytic ethanol oxidation (3.58 A·mgAu+Pt−1), 4.4 times higher than that of commercial Pt/C. This work not only explores the unique asymmetrical effect in the OD of ternary intermetallics, but also helps to understand the complex inter‐metallic relationship in the medium‐entropy and high‐entropy alloys.
A Non‐Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS/TGF‐β1 Signaling
Authors: Liu Ruxia , Zhou Ting , Li Xinsheng , Zou Quan , Yu Jiaojiao , Ye Jingjing , Wang Wenhui , Zhou Yan , Sun Shao‐Kai
Published: August 2024

Pulmonary hypertension (PH) is a life‐threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non‐metallic nanozyme is reported for the treatment of monocrotaline (MCT)‐induced PH with a therapeutic mechanism involving the ROS/TGF‐β1 signaling. The synthesized melanin‐polyvinylpyrrolidone‐polyethylene glycol (MPP) nanoparticles showcase ultra‐small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT‐PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS‐driven activation of TGF‐β1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non‐metallic nanozymes based on a well‐understood mechanism.
3D Bioprinted Tissue‐Engineered Bone with Enhanced Mechanical Strength and Bioactivities: Accelerating Bone Defect Repair through Sequential Immunomodulatory Properties
Authors: Liu Daqian , Liu Jingsong , Zhao Pengcheng , Peng Zhibin , Geng Zhibin , Zhang Jingwei , Zhang Zhuoran , Shen Ruifang , Li Xiang , Wang Xiaoyu , Li Shuangzuo , Wang Jiankai , Wang Xintao
Published: August 2024

In this study, a new‐generation tissue‐engineered bone capable of temporally regulating the immune response, balancing proinflammatory and anti‐inflammatory activities, and facilitating bone regeneration and repair to address the challenges of delayed healing and nonunion in large‐sized bone defects, is innovatively developed. Using the innovative techniques including multiphysics‐assisted combined decellularization, side‐chain biochemical modification, and sterile freeze‐drying, a novel photocurable extracellular matrix hydrogel, methacrylated bone‐derived decellularized extracellular matrix (bdECM‐MA), is synthesized. After incorporating the bdECM‐MA with silicon‐substituted calcium phosphate and bone marrow mesenchymal stem cells, the tissue‐engineered bone is fabricated through digital light processing 3D bioprinting. This study provides in vitro confirmation that the engineered bone maintains high cellular viability while achieving MPa‐level mechanical strength. Moreover, this engineered bone exhibits excellent osteogenesis, angiogenesis, and immunomodulatory functions. One of the molecular mechanisms of the immunomodulatory function involves the inhibition of the p38‐MAPK pathway. A pioneering in vivo discovery is that the natural biomaterial‐based tissue‐engineered bone demonstrates sequential immunomodulatory properties that activate proinflammatory and anti‐inflammatory responses in succession, significantly accelerating the repair of bone defects. This study provides a new research basis and an effective method for developing autogenous bone substitute materials and treating large‐sized bone defects.