bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of testing modality on bioefficacy for the evaluation of Interceptor® G2 mosquito nets to combat malaria mosquitoes in Tanzania
Authors: Kibondo Ummi Abdul , Odufuwa Olukayode G. , Ngonyani Saphina H. , Mpelepele Ahmadi B. , Matanilla Issaya , Ngonyani Hassan , Makungwa Noel O. , Mseka Antony P. , Swai Kyeba , Ntabaliba Watson , Stutz Susanne , Austin James W. , Moore Sarah Jane
Published: April 2022

Background

Insecticide-treated net (ITN) durability is evaluated using longitudinal bioefficacy and fabric integrity sampling post-distribution. Interceptor® G2 was developed for resistance management and contains two adulticides: alpha-cypermethrin and chlorfenapyr; it is a pro-insecticide that is metabolized into its active form by mosquito-detoxifying enzymes and may be enhanced when the mosquito is physiologically active. To elucidate the impact of bioassay modality, mosquito exposures of the alphacypermethrin ITN Interceptor® and dual adulticide Interceptor® G2 were investigated.

Methods

This study evaluated the performance of Interceptor® G2 compared to Interceptor® against local strains of mosquitoes in Tanzania. Unwashed and 20× times washed nets were tested. Efficacy of ITNs was measured by four bioassay types: (1) World Health Organisation (WHO) cone test (cone), (2) WHO tunnel test (tunnel), (3) Ifakara ambient chamber test (I-ACT) and (4) the WHO gold standard experimental hut test (hut). Hut tests were conducted against free-flying wild pyrethroid metabolically resistant Anopheles arabiensis and Culex quinquefasciatus. Cone, tunnel and I-ACT bioassays used laboratory-reared metabolically resistant An. arabiensis and Cx. quinquefasciatus and pyrethroid susceptible Anopheles gambiae sensu stricto and Aedes aegypti.

Results

Against resistant strains, superiority of Interceptor® G2 over Interceptor® was observed in all “free-flying bioassays”. In cone tests (which restrict mosquito flight), superiority of Interceptor® over Interceptor® G2 was recorded. Mortality of unwashed Interceptor® G2 among An. arabiensis was lowest in hut tests at 42.9% (95% CI: 37.3–48.5), although this increased to 66.7% (95% CI: 47.1–86.3) by blocking hut exit traps so mosquitoes presumably increased frequencies of contact with ITNs. Higher odds of mortality were consistently observed in Interceptor® G2 compared to Interceptor® in “free-flying” bioassays using An. arabiensis: tunnel (OR = 1.42 [95% CI:1.19–1.70], p < 0.001), I-ACT (OR = 1.61 [95% CI: 1.05–2.49], p = 0.031) and hut (OR = 2.53 [95% CI: 1.96–3.26], p < 0.001). Interceptor® and Interceptor® G2 showed high blood-feeding inhibition against all strains.

Conclusion

Both free-flying laboratory bioassays (WHO Tunnel and I-ACT) consistently measured similarly, and both predicted the results of the experimental hut test. For bioefficacy monitoring and upstream product evaluation of ITNs in situ, the I-ACT may provide an alternative bioassay modality with improved statistical power. Interceptor G2® outperformed Interceptor ® against pyrethroid-resistant strains, demonstrating the usefulness of chlorfenapyr in mitigation of malaria.

Graphical Abstract
Five weeks of Yuishinkai karate training improves balance and neuromuscular function in older adults: a preliminary study
Authors: Mustafa Hajer , Harrison Aimee , Sun Yao , Pearcey Gregory E. P. , Follmer Bruno , Nazaroff Benjamin M. , Rhodes Ryan E. , Zehr E. Paul
Published: April 2022

Background

Martial arts training has shown positive impacts on balance and physiological measurements. Further investigation of the contents and feasibility of an effective therapeutic assessment of martial arts is needed in older adults, mainly for future applications and real-world implementation.

Methods

Sixteen older adults (8 male, 8 female, age 59–90 years), with or without chronic conditions, participated in a preliminary study using 5-weeks of karate training and a triple baseline control procedure. Group and single subject data analyses were conducted for dynamic balance, Timed Up and Go (TUG), hand grip, ankle plantarflexion force, and spinal cord excitability (via the soleus H-reflex) pre- and post-training.

Results

On average, participants completed a total of 2437 steps, 1762 turns, 3585 stance changes, 2047 punches, 2757 blocks, and 1253 strikes. Karate training improved dynamic balance performance such that the group average time was reduced (time to target (−13.6%, p = 0.020) and time to center (−8.3%, p = 0.010)). TUG was unchanged when considering the entire group (p = 0.779), but six participants displayed significant changes. Left handgrip (7.9%, p = 0.037), and plantarflexion force in the right (28.8%, p = 0.045) and left leg (13.3%, p = 0.024) increased for the group. Spinal cord excitability remained unchanged in group data analysis but 5 individuals had modulated Hmax/Mmax ratios.

Conclusion

5-weeks of karate training delivered in a fashion to mimic generally accessible community-level programs improved balance and strength in older adults. Whole-body movement embodied in karate training enhanced neuromuscular function and postural control. We met the overriding goal of this preliminary study to emphasize and assess feasibility and safety for the generalizability of martial arts interventions to real-world communities to impact health outcomes. Further quantitative work should explore threshold dose and development of martial arts training interventions as potential “exercise is medicine” functional fitness for older adults.
Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
Authors: Good Misty , Chu Tianjiao , Shaw Patricia , Nolan Lila S. , Wrobleski Joseph , Castro Carlos , Gong Qingqing , DeWitt Olivia , Finegold David N. , Peters David
Published: April 2022

Objective

Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.

Design

To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth.

Results

We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants.

Conclusion

We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC.
Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy
Authors: Pan Tingcai , Wang Ning , Zhang Jiaye , Yang Fan , Chen Yan , Zhuang Yuanqi , Xu Yingying , Fang Ji , You Kai , Lin Xianhua , Li Yang , Li Shao , Liang Kangyan , Li Yin-xiong , Gao Yi
Published: April 2022

Background

Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable.

Methods

We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.

Results

We demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo.

Conclusion

Our current small-molecule-based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.
Breast carcinoma-amplified sequence 2 regulates adult neurogenesis via β-catenin
Authors: Chen Hsin-Hsiung , Lu Hao-Yu , Chang Chao-Hsin , Lin Shih-Hao , Huang Chu-Wei , Wei Po-Han , Chen Yi-Wen , Lin Yi-Rou , Huang Hsien-Sung , Wang Pei-Yu , Tsao Yeou-Ping , Chen Show-Li
Published: April 2022

Background

Breast carcinoma-amplified sequence 2 (BCAS2) regulates β-catenin gene splicing. The conditional knockout of BCAS2 expression in the forebrain (BCAS2 cKO) of mice confers impaired learning and memory along with decreased β-catenin expression. Because β-catenin reportedly regulates adult neurogenesis, we wondered whether BCAS2 could regulate adult neurogenesis via β-catenin.

Methods

BCAS2-regulating neurogenesis was investigated by characterizing BCAS2 cKO mice. Also, lentivirus-shBCAS2 was intracranially injected into the hippocampus of wild-type mice to knock down BCAS2 expression. We evaluated the rescue effects of BCAS2 cKO by intracranial injection of adeno-associated virus encoding BCAS2 (AAV-DJ8-BCAS2) and AAV-β-catenin gene therapy.

Results

To show that BCAS2-regulating adult neurogenesis via β-catenin, first, BCAS2 cKO mice showed low SRY-box 2-positive (Sox2+) neural stem cell proliferation and doublecortin-positive (DCX+) immature neurons. Second, stereotaxic intracranial injection of lentivirus-shBCAS2 knocked down BCAS2 in the hippocampus of wild-type mice, and we confirmed the BCAS2 regulation of adult neurogenesis via β-catenin. Third, AAV-DJ8-BCAS2 gene therapy in BCAS2 cKO mice reversed the low proliferation of Sox2+ neural stem cells and the decreased number of DCX+ immature neurons with increased β-catenin expression. Moreover, AAV-β-catenin gene therapy restored neuron stem cell proliferation and immature neuron differentiation, which further supports BCAS2-regulating adult neurogenesis via β-catenin. In addition, cells targeted by AAV-DJ8 injection into the hippocampus included Sox2 and DCX immature neurons, interneurons, and astrocytes. BCAS2 may regulate adult neurogenesis by targeting Sox2+ and DCX+ immature neurons for autocrine effects and interneurons or astrocytes for paracrine effects.

Conclusions

BCAS2 can regulate adult neurogenesis in mice via β-catenin.
Menstrual blood-derived mesenchymal stromal cells efficiently ameliorate experimental autoimmune encephalomyelitis by inhibiting T cell activation in mice
Authors: Li Yonghai , Gao Haiyao , Brunner Tobias M. , Hu Xiaoxi , Yan Yushan , Liu Yanli , Qiao Liang , Wu Peihua , Li Meng , Liu Qing , Yang Fen , Lin Juntang , Löhning Max , Shen Ping
Published: April 2022

Background

Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE).

Methods

We assessed the therapeutic effect of MB-MSCs transplanted via either intravenous (i.v.) or intraperitoneal (i.p.) route in EAE in comparison with umbilical cord-derived MSCs (UC-MSCs). We used histology to assess myelin sheath integrity and infiltrated immune cells in CNS and flow cytometry to evaluate EAE-associated inflammatory T cells and antigen-presenting cells in lymphoid organs.

Results

We observed disease-ameliorating effects of MB-MSCs when transplanted at various stages of EAE (day − 1, 6, 10, and 19), via either i.v. or i.p. route, with a potency comparable to UC-MSCs. We observed reduced Th1 and Th17 cell responses in mice that had received MB-MSCs via either i.v. or i.p. injection. The repressed Th1 and Th17 cell responses were associated with a reduced frequency of plasmacytoid dendritic cells (pDCs) and a suppressed co-stimulatory capacity of pDCs, cDCs, and B cells.

Conclusions

Our data demonstrate that the readily available MB-MSCs significantly reduced the disease severity of EAE upon transplantation. Thus, they have the potential to be developed as ready-to-use allo-MSCs in MS-related inflammation.

Graphical abstract
Estimation of playable piano fingering by pitch-difference fingering match model
Authors: Guan Xin , Zhao Haoyue , Li Qiang
Published: April 2022

Most existing statistical models used to predict piano fingering apply explicit constraints among fingers and between fingers and notes; however, they disregard the relationship among notes. Furthermore, the state transfer matrix of HMM often makes the fingering of notes in compact scales unplayable without moving the hands. The direct adoption of notes interferes with mapping between specific pitches and the corresponding fingering. Inspired by human annotation and the note span constraints used in rule-based methods (in which fingering knowledge is acquired from span), we developed a model by which to match pitch difference and finger sequences (PdF). Playable fingering is achieved by combining learned finger-transfer knowledge with priori finger-transfer knowledge. The playability of the model was evaluated using a novel index, referred to as the irrational fingering rate (IFR). Experiment results demonstrate that the proposed model outperforms the third-order hidden Markov finger annotation model in terms of average match rate (by 4.06%) and highest match rate (by 2.87%). The proposed scheme also resolves the unplayable-without-hand-movement problem in compact scales.
Some parameterized Simpson-, midpoint- and trapezoid-type inequalities for generalized fractional integrals
Authors: Budak Hüseyin , Kılınç Yıldırım Seda , Sarıkaya Mehmet Zeki , Yıldırım Hüseyin
Published: April 2022

In this paper, we first obtain an identity for differentiable mappings. Then, we establish some new generalized inequalities for differentiable convex functions involving some parameters and generalized fractional integrals. We show that these results reduce to several new Simpson-, midpoint- and trapezoid-type inequalities. The results given in this study are the generalizations of results proved in several earlier papers.
Multiple solutions for a system involving an anisotropic variable exponent operator
Authors: Tavares Leandro S.
Published: April 2022

In this paper, the existence of a solution for an anisotropic variable exponent system is obtained and proved under general hypotheses. By considering additional conditions, it is proved a multiplicity result. The proofs are based on an application of appropriated $L^{\infty }$

L
∞

estimates, a sub-supersolution argument, and the Mountain Pass Theorem.
Interspecies microbiome transplantation recapitulates microbial acquisition in mosquitoes
Authors: Coon Kerri L. , Hegde Shivanand , Hughes Grant L.
Published: April 2022

Background

Mosquitoes harbor microbial communities that play important roles in their growth, survival, reproduction, and ability to transmit human pathogens. Microbiome transplantation approaches are often used to study host-microbe interactions and identify microbial taxa and assemblages associated with health or disease. However, no such approaches have been developed to manipulate the microbiota of mosquitoes.

Results

Here, we developed an approach to transfer entire microbial communities between mosquito cohorts. We undertook transfers between (Culex quinquefasciatustoAedes aegypti) and within (Ae. aegyptitoAe. aegypti) species to validate the approach and determine the number of mosquitoes required to prepare donor microbiota. After the transfer, we monitored mosquito development and microbiota dynamics throughout the life cycle. Typical holometabolous lifestyle-related microbiota structures were observed, with higher dynamics of microbial structures in larval stages, including the larval water, and less diversity in adults. Microbiota diversity in recipient adults was also more similar to the microbiota diversity in donor adults.

Conclusions

This study provides the first evidence for successful microbiome transplantation in mosquitoes. Our results highlight the value of such methods for studying mosquito-microbe interactions and lay the foundation for future studies to elucidate the factors underlying microbiota acquisition, assembly, and function in mosquitoes under controlled conditions.
Time-dependent memory and individual variation in Arctic brown bears (Ursus arctos)
Authors: Thompson Peter R. , Lewis Mark A. , Edwards Mark A. , Derocher Andrew E.
Published: April 2022

Background

Animal movement modelling provides unique insight about how animals perceive their landscape and how this perception may influence space use. When coupled with data describing an animal’s environment, ecologists can fit statistical models to location data to describe how spatial memory informs movement.

Methods

We performed such an analysis on a population of brown bears (Ursus arctos) in the Canadian Arctic using a model incorporating time-dependent spatial memory patterns. Brown bear populations in the Arctic lie on the periphery of the species’ range, and as a result endure harsh environmental conditions. In this kind of environment, effective use of memory to inform movement strategies could spell the difference between survival and mortality.

Results

The model we fit tests four alternate hypotheses (some incorporating memory; some not) against each other, and we found a high degree of individual variation in how brown bears used memory. We found that 71% (15 of 21) of the bears used complex, time-dependent spatial memory to inform their movement decisions.

Conclusions

These results, coupled with existing knowledge on individual variation in the population, highlight the diversity of foraging strategies for Arctic brown bears while also displaying the inference that can be drawn from this innovative movement model.
Does vitamin D have an effect on osseointegration of dental implants? A systematic review
Authors: Werny Joscha G. , Sagheb Keyvan , Diaz Leonardo , Kämmerer Peer W. , Al-Nawas Bilal , Schiegnitz Eik
Published: April 2022

Purpose

The aim of this study was to systematically review the available evidence to evaluate the efficacy of vitamin D supplementation or vitamin D depletion on the osseointegration of implants in animals and humans.

Methods

The focus questions addressed were “Do vitamin D deficient subjects treated with (dental) implants have an inferior osseointegration than subjects with adequate serum vitamin D level?” and “Do vitamin D supplemented subjects treated with (dental) implants have a superior osseointegration than subjects with adequate serum vitamin D level?” Humans and animals were considered as subjects in this study. Databases were searched from 1969 up to and including March 2021 using different combination of the following terms: “implant”, “bone to implant contact”, “vitamin D” and “osseointegration”. Letters to the editor, historic reviews, commentaries and articles published in languages other than English and German were excluded. The pattern of the present systematic review was customize to primarily summarize the pertinent data.

Results

Thirteen experimental studies with animals as subject, two clinical studies and three case reports, with humans as subjects, were included. The amount of inserted titanium implants ranged between 24 and 1740. Results from three animal studies showed that vitamin D deficiency has a negative effect on new bone formation and/or bone to implant contact (BIC). Eight animal studies showed that vitamin D supplementation has a enhancing effect on BIC and/or new bone formation around implants. Furthermore, enhancing the impact of vitamin D supplementation on the osseointegration of implants in subjects with diabetes mellitus, osteoporosis and chronic kidney disease (CKD) were assessed. Studies and case reports involving human subjects showed that patients with a low serum vitamin D level have a higher tendency to exhibit an early dental implant failure. When supplemented with vitamin D the osseointegration was successful in the case reports and a beneficial impact on the changes in the bone level during the osseointegration were determined.

Conclusions

Vitamin D deficiency seems to have a negative effect on the osseointegration of implants in animals. The supplementation of vitamin D appears to improve the osseointegration in animals with systemic diseases, such as vitamin D deficiency, diabetes mellitus, osteoporosis, and CKD. Slight evidence supports the hypothesis that humans similarly benefit from vitamin D supplementation in terms of osseointegration. Further investigation is required to maintain these assumptions.
Role of pudendal nerve block for prevention of catheter-related bladder discomfort in male pediatric patients undergoing hypospadias surgery: a prospective randomized control study
Authors: Rath Amrita , Reena
Published: April 2022

Background

Catheter-related bladder discomfort (CRBD) is a common distressing symptom complex during the postoperative period, especially after urologic procedures followed by urinary catheterization. The purpose of this study is to evaluate the efficacy of pudendal nerve block and compare it with intravenous butylscopolamine in CRBD prevention in pediatric male patients undergoing hypospadias surgery under general anesthesia.

Results

After getting ethical committee clearance and informed written consent, 60 male pediatric patients scheduled for hypospadias repair were enrolled for the study and were randomized using computer-generated random numbers in 2 groups of 30 each: group P (received bilateral pudendal nerve block using 0.25% ropivacaine) and group B (received intravenous butylscopolamine 0.3 mg/kg) 15 min before extubation. The primary outcome was the incidence and severity of CRBD. Visual analog scale (VAS) for postoperative pain, postoperative side effects, the postoperative requirement for tramadol as a rescue treatment for CRBD and fentanyl as rescue analgesia for postoperative pain, and VAS for acceptance of an indwelling urinary catheter were the secondary outcomes. The incidences of CRBD and side effects were analyzed by the chi-square test and severity by Fisher’s exact test. The VAS scale was analyzed by the Mann-Whitney test. A p value of < 0.05 was considered significant.

Group P had significantly decreased incidence as well as severity of postoperative CRBD than group B with p < 0.05. The postoperative median VAS score and number of patients requiring fentanyl as rescue analgesics were significantly low in group P in comparison with group B (p < 0.05). The total tramadol requirement at the end of 6 h for CRBD management was also significantly reduced in group P (p < 0.0001).

Conclusions

Pudendal nerve block seems to be superior to intravenous butylscopolamine in reducing the incidence and severity of CRBD. This study can be extrapolated to other urogenital studies in pediatric patients.
Subsurface temperature prediction by means of the coefficient correction method of the optimal temperature: A case study in the Xiong’an New Area, China
Authors: Huang Guoshu , Hu Xiangyun , Cai Jianchao , Ma Huolin , Chen Bin , Liao Chen , Zhang Shihui , Zhou Wenlong
Published: April 2022

Accurate estimation of the earth’s interior temperature is extremely important for studying fundamental scientific and applied geothermal problems. Existing temperature estimation methods cannot provide reliable accuracy in the cross-borehole space and beyond the borehole’s depth; however, resistivity could overcome this difficulty as a temperature-dependent proxy parameter. At present, this approach is based on the use of purely empirical formulas, whose validity is unjustifiably postulated to be invariant with respect to geologic settings. We develop an electromagnetic (EM) geothermometer based on the coefficient correction method of the optimal temperature (CCMOT). This geothermometer can accurately determine the relationship between the normalized resistivity and temperature in an underground space based on resistivity-temperature logging data and EM data; therefore, a visualized temperature distribution can be calculated. The CCMOT is applied to the subsurface temperature prediction in the Xiong’an New Area, with an accuracy of 86.69%–97.25%. Sensitivity analysis of the key variables of the CCMOT reveal that the CCMOT has relatively little dependence on the number of constraining boreholes and the optimization of the subdivision spacing of the logging data can significantly improve temperature prediction accuracy. The CCMOT can be used to determine the distribution of the heat structure of the reservoir and to interpret the geothermal field. In addition, the CCMOT is of great significance to the evaluation, scientific development, and sustainable use of geothermal resources.
A new generation low-frequency seismic vibrator
Authors: Wei Zhouhong , Criss Jason , Wang Rong , Clow Alistair
Published: April 2022

Extending the vibroseis acquisition bandwidth toward very low frequencies (below 5 Hz) can be very beneficial for land seismic exploration. However, most conventional hydraulic vibrators have physical limitations as well as harmonic distortion in the vibrator mechanical and hydraulic systems that limit the ground-force output at low frequencies. To enhance the low-frequency range, the vibrator output force must be increased with an improved signal-to-noise ratio. An improved design of the vibrator mechanical and hydraulic system becomes very necessary to achieve this goal. With this goal, a newly designed low-frequency vibrator is developed and field-tested. Experimental results find that this new generation low-frequency vibrator can produce the recoverable seismic data with a low-frequency range from 1 to 4 Hz.
Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2– Early Breast Cancer
Authors: Nitz Ulrike A. , Gluz Oleg , Kümmel Sherko , Christgen Matthias , Braun Michael , Aktas Bahriye , Lüdtke-Heckenkamp Kerstin , Forstbauer Helmut , Grischke Eva-Maria , Schumacher Claudia , Darsow Maren , Krauss Katja , Nuding Benno , Thill Marc , Potenberg Jochem , Uleer Christoph , Warm Mathias , Fischer Hans Holger , Malter Wolfram , Hauptmann Michael , Kates Ronald E. , Gräser Monika , Würstlein Rachel , Shak Steven , Baehner Frederick , Kreipe Hans H. , Harbeck Nadia
Published: April 2022

PURPOSE

To our knowledge, WSG-ADAPT-HR+/HER2– (ClinicalTrials.gov identifier: NCT01779206 ; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer.

MATERIALS AND METHODS

Baseline and postendocrine Ki67 (Ki67post) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( v control) arm; secondary end points included distant DFS, overall survival, and translational research.

RESULTS

Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was –3.3%, establishing prespecified noninferiority ( P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001).

CONCLUSION

WSG-ADAPT-HR+/HER2– demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
Transient accumulation and bidirectional movement of KIF13B in primary cilia
Authors: Juhl Alice Dupont , Anvarian Zeinab , Kuhns Stefanie , Berges Julia , Andersen Jens S. , Wüstner Daniel , Pedersen Lotte B.
Published: April 2022

Primary cilia are microtubule-based sensory organelles whose assembly and function rely on the conserved bidirectional intraflagellar transport (IFT) system, which is powered by anterograde kinesin-2 and retrograde cytoplasmic dynein-2 motors. Nematodes additionally employ a cell-type-specific kinesin-3 motor, KLP-6, which moves within cilia independently of IFT and regulates ciliary content and function. Here, we provide evidence that a KLP-6 homolog, KIF13B, undergoes bursts of bidirectional movement within primary cilia of cultured immortalized human retinal pigment epithelial (hTERT-RPE1) cells. Anterograde and retrograde intraciliary velocities of KIF13B were similar to those of IFT (as assayed using IFT172–eGFP), but intraciliary movement of KIF13B required its own motor domain and appeared to be cell-type specific. Our work provides the first demonstration of motor-driven, intraciliary movement by a vertebrate kinesin other than kinesin-2 motors.
Escaping from multiple visual threats: modulation of escape responses in Pacific staghorn sculpin (Leptocottus armatus)
Authors: Kimura Hibiki , Pfalzgraff Tilo , Levet Marie , Kawabata Yuuki , Steffensen John F. , Johansen Jacob L. , Domenici Paolo
Published: April 2022

Fish perform rapid escape responses to avoid sudden predatory attacks. During escape responses, fish bend their bodies into a C-shape and quickly turn away from the predator and accelerate. The escape trajectory is determined by the initial turn (stage 1) and a contralateral bend (stage 2). Previous studies have used a single threat or model predator as a stimulus. In nature, however, multiple predators may attack from different directions simultaneously or in close succession. It is unknown whether fish are able to change the course of their escape response when startled by multiple stimuli at various time intervals. Pacific staghorn sculpin (Leptocottus armatus) were startled with a left and right visual stimulus in close succession. By varying the timing of the second stimulus, we were able to determine when and how a second stimulus could affect the escape response direction. Four treatments were used: a single visual stimulus (control); or two stimuli coming from opposite sides separated by a 0 ms (simultaneous treatment), 33 ms or 83 ms time interval. The 33 ms and 83 ms time intervals were chosen to occur either side of a predicted 60 ms visual escape latency (i.e. during stage 1). The 0 ms and 33 ms treatments influenced both the escape trajectory and the stage 1 turning angle, compared with a single stimulation, whereas the 83 ms treatment had no effect on the escape trajectory. We conclude that Pacific staghorn sculpin can modulate their escape trajectory only between stimulation and the onset of the response, but the escape trajectory cannot be modulated after the body motion has started.
Ενίσχυση ετοιμότητας ψηφιακής εγκληματολογικής διερεύνησης με τη χρήση κυβερνογνώσης
Authors: Σερκετζής Νικόλαος
Published: April 2022

Το διαδίκτυο αποτελεί ομολογουμένως ένα από τα σημαντικότερα τεχνολογικά επιτεύγματα της σύγχρονης εποχής. Η καθολική σχεδόν αποδοχή του και η εκτενής εξάρτηση από αυτό το έθεσαν στο επίκεντρο του ενδιαφέροντος κυβερνοεγκληματιών που επιτίθενται, σε καθημερινή βάση, στα μέσω αυτού διασυνδεδεμένα πληροφοριακά συστήματα. Τόσο η ερευνητική κοινότητα όσο και η βιομηχανία βρίσκονται τα τελευταία χρόνια σε μία συνεχή προσπάθεια προάσπισης των πληροφοριακών αυτών συστημάτων. Τα αντίθετα ωστόσο συμφέροντα επιτιθέμενων και αμυνομένων καθιστούν τον τομέα της ασφάλειας έναν καθημερινό στίβο μάχης.Παρά τις συνεχείς βελτιώσεις των μηχανισμών ασφαλείας πληροφοριακών συστημάτων, οι θιασώτες των παραβατικών διαδικτυακών συμπεριφορών επιτυγχάνουν σε αρκετές περιπτώσεις να τα παρακάμπτουν, εκμεταλλευόμενοι μάλιστα αρκετές φορές και τα τρωτά σημεία της ανθρώπινης συμπεριφοράς. Η απορρέουσα λοιπόν, από τέτοια γεγονότα, ανάγκη για αναγνώριση και βελτίωση των όποιων παθογενειών των μηχανισμών άμυνας, έθεσε τα θεμέλια για την ανάπτυξη του τομέα της εγκληματολογικής πληροφορικής (Digital Forensics) αρχικά και της ετοιμότητας ψηφιακής εγκληματολογικής διερεύνησης (Digital Forensic Readiness) στη συνέχεια. Η πρώτη εστιάζει στη συλλογή και ανάλυση ψηφιακών ιχνών, τα οποία ενδεχομένως να έχουν καταγραφεί, ενώ η δεύτερη επενδύει σε πρώιμες διαδικασίες ενίσχυσης της συλλογής και ανάλυσης τους με απώτερο στόχο την ταχύτερη εξαγωγή συμπερασμάτων και κατά συνέπεια λήψη διορθωτικών μέτρων.Αναγνωρίζοντας λοιπόν την ανάγκη για ανάπτυξη ταχύτερων διαδικασιών ψηφιακής εγκληματολογικής διερεύνησης, η παρούσα διατριβή επικεντρώνει το ενδιαφέρον της στη μελέτη θεμάτων παραβίασης της Ασφάλειας Πληροφοριακών Συστημάτων και ενίσχυσης των τεχνικών εγκληματολογικής πληροφορικής.Σκοπός της παρούσας έρευνας είναι η ανάπτυξη ενός μεθοδολογικού πλαισίου και τεχνικών που θα συνεισφέρουν ουσιαστικά στη βελτίωση του επιπέδου της ετοιμότητας ψηφιακής εγκληματολογικής διερεύνησης, μέσω καινοτόμων διαδικασιών ανάλυσης υφιστάμενης κυβερνογνώσης (Cyber Threat Intelligence).Βασικός λοιπόν στόχος και συνεισφορά της παρούσας διατριβής είναι η μετακύλιση, μέσω του προτεινόμενου μεθοδολογικού πλαισίου, του οφέλους της κυβερνογνώσης που συχνά χρησιμοποιείται ως μέσον ενίσχυσης των τεχνολογιών άμυνας, στο στάδιο της ενίσχυσης των διαδικασιών αντιμετώπισης συμβάντων και θεραπείας.
Minimization of Total Variable Cost through Determination of Batch Transfer Size at m Serial CNC-Machining Centers
Authors: R Muhammad Chaznin , Nu'man A Harits
Published: April 2022

Background: In a batch production series consisting of several process stages for discrete products, the determination of the transfer batch size greatly affects the batch waiting time. For production using a Computer Numerical Control (CNC)-machining center, several process stages can be carried out on one machine with quick setup. The use of a single machine for all stages of the process certainly does not require transfer to the next machine. Thus, there are no material handling costs. However, the use of a single machine will result in longer batch waiting times as the production batch size increases. An increase in the batch waiting time will result in an increase in work-in-process (WIP) inventory cost. This research was conducted to reduce the total variable cost consisting of WIP inventory cost and material handling cost.

Methods: This research was conducted in two steps. The first step is to divide the process stages, I into m serial CNC machining centers, where in this study I=m. The second step is to determine the same size of transfer batch, Qij for a certain number of transfers, J that produces the minimum total variable cost.

Results: The results showed that J=5 resulted in a total variable cost of Rp. 146,800.00, while J=10 resulted in a total variable cost of Rp. 178,900.00.

Conclusion: In conclusion, the total variable cost decreases if the size of transfer batch is reduced to a certain amount and will increase again along with the reduction in the size of transfer batch.
Machine learning methods to predict particulate matter PM2.5
Authors: Palanichamy Naveen , Haw Su-Cheng , S Subramanian , Murugan Rishanti , Govindasamy Kuhaneswaran
Published: April 2022

Introduction

Pollution of air in urban cities across the world has been steadily increasing in recent years. An increasing trend in particulate matter, PM2.5, is a threat because it can lead to uncontrollable consequences like worsening of asthma and cardiovascular disease. The metric used to measure air quality is the air pollutant index (API). In Malaysia, machine learning (ML) techniques for PM2.5 have received less attention as the concentration is on predicting other air pollutants. To fill the research gap, this study focuses on correctly predicting PM2.5 concentrations in the smart cities of Malaysia by comparing supervised ML techniques, which helps to mitigate its adverse effects.

Methods

In this paper, ML models for forecasting PM2.5 concentrations were investigated on Malaysian air quality data sets from 2017 to 2018. The dataset was preprocessed by data cleaning and a normalization process. Next, it was reduced into an informative dataset with location and time factors in the feature extraction process. The dataset was fed into three supervised ML classifiers, which include random forest (RF), artificial neural network (ANN) and long short-term memory (LSTM). Finally, their output was evaluated using the confusion matrix and compared to identify the best model for the accurate prediction of PM2.5.

Results

Overall, the experimental result shows an accuracy of 97.7% was obtained by the RF model in comparison with the accuracy of ANN (61.14%) and LSTM (61.77%) in predicting PM2.5.

Discussion

RF performed well when compared with ANN and LSTM for the given data with minimum features. RF was able to reach good accuracy as the model learns from the random samples by using decision tree with the maximum vote on the predictions.
A note on the equality of the BLUPs for new observations under two linear models
Authors: Haslett Stephen J. , Puntanen Simo
Published: April 2022

We consider two linear models, L_1 and L_2, say, with new unobserved future observations. We give necessary and sufficient conditions in the general situation, without any rank assumptions, that the best linear unbiased predictor (BLUP) of the new observation under the the model L_1 continues to be BLUP also under the model L_2.
BATH MASSAGE
Authors: Ogui Victor
Published: April 2022

Эта книга - настоящий подарок для всех любителей бани! В ней даны подробно иллюстрированные пошаговые инструкции проведения различных видов банного массажа. Для каждой бани (русской парной, финской сауны, турецкой бани хаммам) подобраны самые эффективные массажные технологии - русский веничный, турецкий мыльный, японский с бамбуковыми вениками. Массажные процедуры, проверенные веками, и авторские методики сделают каждый поход в баню волшебным источником здоровья и удовольствия!
Locational Choice and Secondary Movements from the Perspective of Forced Migrants: A Comparison of the Destinations Luxembourg and Germany
Authors: Glorius Birgit , Nienaber Birte
Published: April 2022

In 2015 and 2016, the enormous increase in asylum seekers travelling along the Balkan Route confronted the Member States of the European Union with an exceptional pressure on national asylum systems. Since then academic literature has revealed a reappraisal of the Common European Asylum System at regulative and policy implementation level, notably regarding the fair distribution of asylum seekers across Member States and regions. Yet we know very little about the locational choices of forced migrants or how those choices evolved and transformed during their journey.

In this paper, we aim to shed light on those decision-making processes and (individual, subjective) locational choices based on the aspiration-ability model, drawing from a series of qualitative interviews with migrants held in Luxembourg and Germany in the context of the H2020 project CEASEVAL. We focus on the migrants’ journeys to their actual recipient countries, highlighting mobility trajectories from the moment of first departure and on the process of decision-making regarding their choice of location. Then, we examine further mobility aspirations, which may lead to secondary mobility within or out of the country of residence. In the concluding section, we discuss the consequences of our findings for migration and asylum politics against the background of the “autonomy of migration” framework.

* This article belongs to a special issue on "Refugee Migration to Europe – Challenges and Potentials for Cities and Regions".
Attracting the Sharks: Corporate Innovation and Securities Class Action Lawsuits
Authors: Kempf Elisabeth , Spalt Oliver
Published: April 2022

This paper provides novel evidence suggesting that securities class action lawsuits, a central pillar of the U.S. litigation and corporate governance system, can constitute an obstacle to valuable corporate innovation. We first establish that valuable innovation output makes firms particularly vulnerable to costly low-quality class action litigation. Exploiting judge turnover in federal courts, we then show that changes in class action litigation risk affect the value and number of patents filed, suggesting firms take into account that risk in their innovation decisions. A new perspective we provide is that innovation success, not only innovation failure, can increase firms’ securities class action litigation risk.

This paper was accepted by Victoria Ivashina, finance.

Funding: E. Kempf gratefully acknowledges financial support from the James S. Kemper Foundation at the University of Chicago Booth School of Business.

Supplemental Material: Data and the internet appendix are available at https://doi.org/10.1287/mnsc.2022.4388 .
A guide to undertaking and understanding blood pressure measurement
Authors: Park Laura , Ford Claire , Allan Jaden
Published: April 2022

This article aims to provide background information on blood pressure. It outlines the anatomy and physiology associated with the skill of blood pressure measurement, and the varying techniques for taking blood pressure readings, both invasively and non-invasively. It further explains the steps for taking a manual blood pressure and provides top tips for carrying out this procedure in clinical practice.
Wound healing in second-degree burns in rats treated with silver sulfadiazine: a systematic review and meta-analysis
Authors: Devi Mohan Vimala , Poornima Velswamy , Sivagnanam Uma Tiruchirapalli
Published: April 2022

Objective:

This study aims to assess the wound healing efficacy in second-degree burns in rats treated with 1% silver sulfadiazine (SSD)—a sulfonamide antibiotic.

Method:

This is a systematic literature review and meta-analysis performed according to the PICO (Population, Intervention, Comparison and Outcomes) strategy.

Results:

The review found 100 studies in PubMed, Web of Science and other search engines. Of these, 70 studies were pre-selected after removing duplicates. After independent analysis by two reviewers, only seven studies met the inclusion criteria for meta-analysis. All studies except one showed faster wound closure by the application of silver sulfadiazine ointment. Using a random effects model, healing was faster in SSD-treated groups when compared to the control group on day 21, with a statistically significant mean difference of –2.72 days (95% confidence interval: –4.99, –0.45) between treatment and control groups (p<0.01).

Conclusion:

The results of this meta-analysis revealed that SSD aided in faster healing of second-degree burns.
Developing a metal powder specification for laser metal deposition
Authors: Clayton Jamie , Markusson Lisa , Östergren Lars
Published: April 2022

Jamie Clayton, operations director, Freeman Technology describes what particle and bulk powder properties need to be measured in order to successfully differentiate alternative supplies for laser metal deposition.
Urinary Albumin Creatinine Ratio has no Significant Association with Retinopathy in Individuals with Type 1 Diabetes Mellitus
Authors: Odhaib Samih Abed , Altemimi Mahmood Thamer , Kassid Omer Mansib , Alidrisi Haider Ayad , Alibrahim Nassar Taha Yaseen , Alhamza Ali Hussein Ali , Budair Ahmed Sabah , Mansour Abbas Ali
Published: April 2022

Background The relationship between diabetic retinopathy (DR) and nephropathy in type 1 diabetes mellitus (T1DM) is controversial. This study assessed the utility of the spot urinary albumin creatinine ratio (UACR) as a parameter for correlating diabetic nephropathy with DR in individuals with T1DM in Basrah. Methods The study was a cross-sectional observational study of 216 patients with T1DM (16–49 years old) with different DR types. We used demographic variables, different T1DM-related variables (onset and duration of T1DM, glycemic control, latency between T1DM and DR onset, age of onset of DR), and biochemical investigations, such as spot UACR, renal function tests, glycated hemoglobin (HbA1c), anti-glutamic acid decarboxylase-65 (anti-GAD-65) antibody, lipid profile, and thyrotropin. We used ordinal regression analysis to test for the possible primary covariates and adjusted the findings with an analysis of covariates (ANCOVA). Results The patient population showed a slight male preponderance, and uncontrolled T1DM with high HbA1c was found in 93% of the cohort. The mean UACR was 64.37 ± 8.99 mg/g. Normal UACR levels were seen in approximately 60% of the cohort (n=129). Sixty-five individuals were reported to have DR, with a median age of onset of 34 ± 8 years and a median latency period of 13 ± 7 years. UACR had no significant relationship with DR development at any association level, with or without adjustment for the composite regression factors. Conclusion There was no significant association between UACR at any level and DR development before and after adjustment for all of the possible covariates in this study.