bluuebunny/crossref_metadata_2025 huggingface dataset:
Software protection and software piracy
Authors: Jha Amit Kumar , Rajan Priyanka
Published: March 2022

This paper explores the dynamic long‐term relationship between software protection and software piracy rates across 108 countries over the period of 20 years (1994–2015), with the help of the ARDL model. The analysis employs a new way of utilising the membership duration of Trade related Intellectual Property Rights agreement and World Intellectual Property Organisation Copyright Treaty agreements of different countries in a panel framework, apart from constructing an index of copyright software protection by focusing on enforcement provisions. The paper overcomes various shortcomings of earlier literatures by thoughtful inclusion of independent variables and methodological techniques. Results show that both copyright software protection and income share a negative long‐term relationship with software piracy. Even the enforcement provisions are important in mitigating software piracy. In addition, the model finds a negative relationship between demand for intellectual property protection and software piracy rates.
Underwater calling behavior in two high‐altitude frog species
Authors: Zheng Y. , Xie F.
Published: March 2022

Underwater calls of frogs are poorly documented, probably because they are usually weak and difficult to detect out of water because the impedance contrast at the water–air interface limits sound transmission. The tympanic middle ear and vocal sacs, which may not be essential for underwater acoustic communication, are often reduced in high‐elevation anurans. In addition to the Andean Telmatobius and Sierra Nevada Rana sierrae, many other highland frog species may vocalize underwater rather than be mute as previously thought. We report evidence from the eastern Tibetan Plateau supporting this speculation. In two species of the megophryid genus Scutiger, breeding males emitted trill‐like calls in series under submerged rocks at elevations of approximately 3700 m a.s.l. Because the few high‐elevation anurans known to vocalize underwater are all highly aquatic, this strategy is possibly used because the signal receivers usually remain in water during the breeding season. The finding of underwater calling in Scutiger characterized by reduced middle ears was partly guided by co‐occurrence of loose skin and underwater vocalization in some frog species and constitutes another independent case of such co‐occurrence. We suggest that the presence/absence of loose skin folds should be routinely included in the morphological descriptions of anurans, because an increased surface/volume ratio facilitates effective cutaneous respiration that is required for metabolically costly underwater behaviors which are usually cryptic to human observers.
Interventional management and surgery of neurogenic lower urinary tract dysfunction in patients with chronic spinal cord injury: A urologist's perspective
Authors: Chen Sheng‐Fu , Kuo Hann‐Chorng
Published: March 2022

Neurogenic lower urinary tract dysfunction (NLUTD) caused by spinal cord injury (SCI) is challenging for urologists. NLUTD not only affects the quality of life but also endangers the upper urinary tract of patients with chronic SCI. Considering that the bladder and urethral function change with time, regular follow‐up of NLUTD is necessary, and any complication should be adequately treated. The first priority of bladder management in patients with chronic SCI manifesting NLUTD should be renal function preservation, followed by the normalization of lower urinary tract function. The quality of life should also be assessed. Patients who have a high risk for impaired renal function should be more frequently identified and investigated. Conservative treatment and pharmacological therapy should be started as early as possible. Intravesical or urethral injections of botulinum toxin A is an alternative treatment for refractory NLUTD. When surgical intervention is necessary, less invasive and reversible procedures should be considered first. Improving patients' quality of life and willingness to undergo bladder management is the most important aspect of treatment.
When does portfolio compression reduce systemic risk?
Authors: Veraart Luitgard Anna Maria
Published: March 2022

We analyze the consequences of portfolio compression for systemic risk. Portfolio compression is a post‐trade netting mechanism that reduces gross positions while keeping net positions unchanged and it is part of the financial legislation in the United States (Dodd–Frank Act) and in Europe (European Market Infrastructure Regulation). We derive necessary structural conditions for portfolio compression to be harmful and discuss policy implications. We show that any potential harmfulness of portfolio compression arises from contagion effects. We show how portfolio compression affects systemic risk depends on the resilience of nodes taking part in compression, on the proportion of debt that they can repay, and on the recovery rates in case of default. In particular, the potential danger of portfolio compression comes from defaults of firms that conduct portfolio compression. If no defaults occur among the firms that engage in compression, then portfolio compression always reduces systemic risk.
Middle East Pre‐Existing Conditions: Regional Security after Covid‐19
Authors: Norlén Tova C.
Published: March 2022

This article analyzes the underlying human insecurities and changing geopolitical alliances in the Middle East during the past decade to assess the most likely short‐ and medium‐term impacts of Covid‐19 on the global security environment. In particular, it focuses on the “pre‐existing conditions” for instability in the Middle East, and the opportunity that the pandemic might have to exacerbate them. The region will likely face a growing regional‐security dilemma compounded by challenges that are now too familiar: the further entrenchment of political authoritarianism, violent sectarian conflicts, regional rivalries, and the radicalization and recruitment efforts by terrorist and extremist groups. While the pandemic has not led to a significant rise in terrorism and extremist violence, it has worsened fragility and accelerated economic decline. This has increased political instability, which, in turn, makes violence more likely. The civil wars in Syria and Yemen, continued threats from Salafi‐Jihadi extremism, massive displacement, sectarianism, and rising inequalities between the rich and the extremely poor are to blame for such fragility. Given the lack of economic resilience and the significant fragility of many Arab states, as well as the availability of advanced military technology in the region, the resulting political, socioeconomic, humanitarian, and security challenges could be devastating.
In with the New: China's Nuclear‐Energy Diplomacy in the Middle East
Authors: Sun Degang , Xu Haiyan , Tu Yichao
Published: March 2022

Nuclear energy, the new frontier of China's cooperation with the Middle East, carries both geoeconomic and geopolitical implications. The development of civil nuclear energy is conducive to the diversification of the energy structure of Middle Eastern countries, meets their increasing needs for electricity at home, and improves their seawater desalinization. Giving full play to its incremental advantage, China's diplomacy strives to expand the market share of its nuclear‐power enterprises in the Middle East, elevate its image as a rising nuclear‐energy power, and advance nuclear‐energy cooperation between China and Saudi Arabia, the UAE, Iran, Algeria, Turkey, Egypt, Jordan, and Sudan through multilateral or bilateral mechanisms. These can be classified into three categories: in‐depth cooperation, active participation, and preliminary exploration. Nuclear‐energy diplomacy aims to expand political influence through civil nuclear activity. Its aim is to enrich the toolkit of China's Middle East diplomacy and is conducive to a multipolar world in terms of civil nuclear research, development, and industries.
Disruptive innovation in psychiatry
Authors: Sarris Jerome
Published: March 2022

Disruptive innovation is a cornerstone of various disciplines, particularly in the business world, where paradigm‐altering approaches are often lauded. As a construct, disruptive psychiatry can be considered to embody such an approach by the pursuit of innovations within the field which test boundaries and shake up the status quo. Given the importance of addressing the current mental health pandemic, and the deficit of highly effective pharmacological treatments for various conditions, innovative disruptive thinking is required. Significant promise exists via the provision of potentially more effective innovative therapeutic options, including digital interventions, psychedelic medicines, microbiome‐altering treatments, brain stimulation technology, and nanotechnology‐based delivery systems. These approaches may be further advanced by individualization of the treatments using computational technology (including quantum computing, machine learning, and artificial intelligence) and genomics.
A trophic cascade causes unexpected ecological interactions across the aquatic–terrestrial interface under extreme weather
Authors: Klatt Björn K. , Pudifoot Bethany , Urrutia‐Cordero Pablo , Smith Henrik G. , Alsterberg Christian M.
Published: March 2022

Trophic cascades in the aquatic environment constitute important mechanisms for improving water quality. However, how the presence or non‐presence of these trophic cascades may affect interactions across the aquatic–terrestrial interface remains poorly investigated. Pollinators such as bees may be especially vulnerable to changes in water resource quality induced by trophic cascades. Understanding how aquatic trophic cascades affect bees and pollination becomes even more pressing under ongoing climate change due to increased physiological demands for water under extreme weather events. In a novel field experiment combining terrestrial and aquatic mesocosms, we aimed to test how changes in water quality induced by an aquatic trophic cascade affected foraging and growth of bumblebee colonies as well as foraging of solitary bees. While we expected fish predation to reduce top–down control of zooplankton on phytoplankton and thereby, indirectly, induce increased growth of toxic cyanobacteria, we instead found the trophic cascade to induce the formation of algal surface mats that bumblebees used to access water under a severe heat wave and drought. This access to water was associated with higher bumblebee colony reproductive success, growth and weight compared to control colonies with no trophic cascade induced (and hence no algal surface mats). We also found marginal but non‐significant effects on oilseed rape yield, but surprisingly with higher yields in the control treatment where bumblebees could not access water. Our results provide new insights on how aquatic trophic cascades can lead to unpredicted ecological interactions across the aquatic–terrestrial interface facilitated by climate change. Our study highlights the importance of water for the fitness of terrestrial ecosystem service providers under altered environmental conditions.
Toward recovery in schizophrenia: Current concepts, findings, and future research directions
Authors: Onitsuka Toshiaki , Hirano Yoji , Nakazawa Takanobu , Ichihashi Kayo , Miura Kenichiro , Inada Ken , Mitoma Ryo , Yasui‐Furukori Norio , Hashimoto Ryota
Published: March 2022

Schizophrenia was initially defined as “dementia praecox” by E. Kraepelin, which implies progressive deterioration. However, recent studies have revealed that early effective intervention may lead to social and functional recovery in schizophrenia. In this review, we provide an overview of current concepts in schizophrenia and pathophysiological hypotheses. In addition, we present recent findings from clinical and basic research on schizophrenia. Recent neuroimaging and neurophysiological studies have consistently revealed specific biological differences in the structure and function of the brain in those with schizophrenia. From a basic research perspective, to determine the essential pathophysiology underlying schizophrenia, it is crucial that findings from all lines of inquiry—induced pluripotent stem cell (iPSC)‐derived neural cells from patients, murine models expressing genetic mutations identified in patients, and patient clinical data—be integrated to contextualize the analysis results. However, the findings remain insufficient to serve as a diagnostic tool or a biomarker for predicting schizophrenia‐related outcomes. Collaborations to conduct clinical research based on the patients' and their families' values are just beginning, and further development is expected.
Exchange through emoting: An emotional model of leader–member resource exchanges
Authors: Liao Zhenyu , Wu Lusi , Zhang Haoyue Jack , Song Zhaoli , Wang Yating
Published: March 2022

Despite research suggesting that emotional interactions pervade daily resource exchanges between leaders and members, the leader–member exchange (LMX) literature has predominantly focused on the interplay between general affective experiences and the overall relationship quality. Drawing upon the affect theory of social exchange, we examine why and how discrete exchange imbalance engenders distinct emotions and shapes downstream work behaviors of the members. Results from a preregistered experimental study with 247 participants and an experience sampling study with time‐lagged reports from 79 leaders and 145 members show that a positively imbalanced exchange increases members’ subsequent leader‐directed helping via gratitude (but not via shame) and that a negatively imbalanced exchange increases members’ subsequent risk‐taking via pride (but not via anger). Moreover, the intensity of such effects hinges upon the average level of resource contributions of leader–member dyads. Our research casts light on the role of transient emotions in dynamic resource exchanges between leaders and members and enriches our knowledge of within‐dyad fluctuations of social exchanges.
Categorical phenomenalism about sexual orientation*
Authors: Whitlow T. R. , Laskowski N. G.
Published: March 2022

What is sexual orientation? The contemporary consensus among philosophers is that it is a disposition. Unsurprisingly, recent debates about the metaphysics of sexual orientation are almost entirely intramural. Behavioral dispositionalists argue that sexual orientation is a disposition to behave sexually. Desire dispositionalists argue that it is a disposition to desire sexually. We argue that sexual orientation is not best understood in terms of dispositions to behave or dispositions to desire before arguing that dispositions tout court fail to illuminate sexual orientation. We then introduce and defend the idea that sexual orientation is best understood in terms of categorical phenomenal properties of sexual arousal.
Characterization of the host range and sensitivity to fungicides of Trichothecium spp. associated with fruit rot in the field and in storage
Authors: Li Yingbin , Liu Yixiang , Zhang Zhiping , Shen Kaiyuan , Hao Jianjun , Luo Laixin , Li Jianqiang
Published: March 2022

During 2017–2019, we observed Trichothecium spp. causing fruit rot in the field and in storage. This study was conducted to examine morphological differences of the species from different hosts, reveal the species’ potential host range, and evaluate the efficacy of five fungicides. Six strains of Trichothecium spp. isolated from nectarine, peach and walnut were selected. Although the colony morphology, mycelial growth rate and spore size differed among hosts, phylogenetic analysis based on the internal transcribed spacer and part of the 5ʹ end of the β‐tubulin gene showed that all tested strains belonged to Trichothecium roseum. For its host range, 23 kinds of fruit were examined using T. roseum strain YT‐1 as an inoculum; 10 kinds of fruit, including pear, apple, mango, Chinese chestnut, pepino melon, fig and durian, were susceptible to T. roseum, with minimum inoculation concentrations ranging from 104 to 105 spores/ml. The fungicides that most effectively inhibited the six isolates were fluazinam and fludioxonil, with EC50 values of 0.07–0.1 and 0.01–0.04 μg/ml, respectively, followed by difenoconazole (0.81–2.96 μg/ml), boscalid (5.43–13.51 μg/ml) and azoxystrobin (9.18–27.25 μg/ml). Improvement of the shelf life of nectarines held in plastic trays was explored using allyl isothiocyanate (AITC) against T. roseum YT‐1. The application of 10 μl/L AITC significantly suppressed disease symptoms. The findings provide useful information for future disease emergency management in the field and for food preservation.
Functional trajectory for the assessment of ecological restoration success
Authors: Manhães Adriana P. , Pantaleão Laura C. , Moraes Luiz F. D. , Amazonas Nino T. , Saavedra Mariana M. , Mantuano Dulce , Sansevero Jerônimo B. B.
Published: March 2022

Ecological restoration aims to recover an ecosystem to a state before degradation. Comparison to reference ecosystems (old‐growth forests) is a key component to define if restoration goals have been achieved (“success”). Nevertheless, it is still unknown how the functional composition of the initial community influences the trajectory of the ecosystem through time. Here, we evaluated restoration success based on the functional trajectory of six 20‐year‐old forest communities planted in the Brazilian Atlantic Forest with distinct combinations of ecological groups (pioneers, secondary, and climax). These six communities ranged their species predominance regarding resource‐use strategies, potential size, and functional diversity. To evaluate restoration success, we compared the functional trajectory between the six planted communities after 20 years of secondary succession and calculated their trajectories toward or away from the reference ecosystem. We found that the initial composition influenced the functional trajectory of the communities undergoing restoration and it was a key element to their success. Only the community planted using the highest functional diversity (i.e. pioneer + early and late secondary + climax species) became functionally similar to the reference ecosystem 20 years after planting. The functional trajectories were mostly driven by the mortality of planted individuals than by the colonization of new species. The regeneration is still functionally similar independently of the treatment evidencing little influence of priority effects in this stage of succession. Our study indicated that the initial functional composition of planted forest communities influences the magnitude and direction of their functional trajectory and may influence restoration success.
A Double-Wiebe Function for Reactivity Controlled Compression Ignition Combustion Using Reformate Diesel
Authors: Yang Ruinan , Ran Zhongnan , Ristow Hadlich Rodrigo , Assanis Dimitris
Published: March 2022

Reactivity controlled compression ignition (RCCI) combustion has previously been proposed as a method to achieve high fuel conversion efficiency and reduce engine emissions. A single-fuel RCCI combustion strategy can have decreased fuel system complexity by using a reformate fuel for port fuel injection and the parent fuel (diesel) for direct injection. This paper presents a one-dimensional computational model of a compression ignition engine with single-fuel RCCI. A Wiebe function is used to predict the combustion process by representing the mass fraction burned (MFB) on a crank angle resolved basis. One single-Wiebe function (SWF) and two double-Wiebe functions(DWFs) were fitted to experimentally derive MFB data using the least-square method. The fitted results were compared with MFBs calculated from experimental data to verify the accuracy. The SWF did not fully capture the MFB curve with high fidelity while the detailed DWF captured the MFB curve within a root mean square error of 1.4%. The reduced double-Wiebe function (RDWF) also resulted in a predicted combustion profile with similar accuracy. Hence, the RDWF was used in a GT-power thermodynamic study to understand the effects of the low-temperature heat release (LTHR) fraction and combustion phasing on combustion characteristics. At optimum phasing of 5–10 crank angle degree after the top dead center, increasing the LTHR fraction from 20% to 60% resulted in the fuel conversion efficiency increasing from 39.5% to 41.1%, thus suggesting that the reformate fuel-based RCCI strategy is viable to unlock improved combustion performance.
Specific Game-Based Performance in Elite Male Adolescent Team Handball Players
Authors: Wagner Herbert , Hinz Matthias , Fuchs Patrick , Bell Jeffrey W. , von Duvillard Serge P.
Published: March 2022

Purpose: In elite team handball, talent identification and selection of the best young players is a fundamental process in several national federations and clubs; however, literature addressing the specific game-based performance in team handball is almost nonexistent. Consequently, the aim of the study was to assess and compare the team-handball-specific game-based performance of elite male team handball players of different ages. Methods: Twelve under-23, 10 under-19, 10 under-17, and 10 under-15 elite male players performed the team-handball game-based performance test. During testing, oxygen uptake, heart rate, sprinting time in defense, offense, fast breaks, and fast retreats, as well as ball velocity and jump height in the jump shot, were measured. Results: Significant differences (P < .05) between under-23, under-19, under-17, and under-15 players were found for absolute peak oxygen uptake, defense, offense and fast break time, ball velocity, and jump height in the game-based performance test, as well as in body weight and height. Conclusion: The results revealed that with increasing age, elite male team handball players are heavier and taller (body weight and height); faster (team-handball offense, defense, and fast break); jump higher and throw faster (in the team-handball jump shot); and perform better aerobically (absolute peak oxygen uptake). The better performance in the under-23 and under-19 players compared with male adult players competing in a lower National Federation league (not on top-elite level) demonstrates that highly specific game-based physical performance determines the potential for developing young male team handball players for competition at the top level.
Relative Contributions of Handgrip and Individual Finger Strength on Climbing Performance in a Bouldering Competition
Authors: Stefan Riley R. , Camic Clayton L. , Miles Garrett F. , Kovacs Attila J. , Jagim Andrew R. , Hill Christopher M.
Published: March 2022

Purpose:To determine the relative contributions of handgrip and individual finger strength for the prediction of climbing performance in a bouldering competition. A secondary aim was to examine the influence of body size, bouldering experience, and training habits.Methods:Sixty-seven boulderers (mean [SD], age = 21.1 [4.0] y; body mass = 69.5 [9.8] kg) volunteered for this study. Data collection occurred immediately before an indoor bouldering competition and involved the assessment of handgrip and individual finger maximal force production using an electronic handheld dynamometer. The bouldering competition consisted of 70 routes graded V0 to V8, with higher point values awarded for completing more difficult routes. Stepwise multiple regression analysis was used to examine the relative contributions of handgrip and individual finger strengths, body mass, height, bouldering experience, and bouldering frequency to the prediction of performance scores in the competition.Results:Ring finger pinch strength, bouldering experience, and bouldering frequency significantly (P < .05) contributed to the model (R2 = .373), whereas body mass; height; full handgrip strength, as well as index, middle, and little finger pinch strengths did not. Theβweights showed that ring finger pinch strength (β = .430) was the most significant contributor, followed by bouldering experience (β = .331) and bouldering frequency (β = .244).Conclusions:The current findings indicated that trainable factors contributed to the prediction of bouldering performance. These results suggest greater bouldering frequency and experience likely contribute to greater isolated individual finger strength, thereby optimizing preparation for the diverse handholds in competitive rock climbing.
The effect of renewable energy incorporation on power grid stability and resilience
Authors: Smith Oliver , Cattell Oliver , Farcot Etienne , O’Dea Reuben D. , Hopcraft Keith I.
Published: March 2022

Contemporary proliferation of renewable power generation is causing an overhaul in the topology, composition, and dynamics of electrical grids. These low-output, intermittent generators are widely distributed throughout the grid, including at the household level. It is critical for the function of modern power infrastructure to understand how this increasingly distributed layout affects network stability and resilience. This paper uses dynamical models, household power consumption, and photovoltaic generation data to show how these characteristics vary with the level of distribution. It is shown that resilience exhibits daily oscillations as the grid’s effective structure and the power demand fluctuate. This can lead to a substantial decrease in grid resilience, explained by periods of highly clustered generator output. Moreover, the addition of batteries, while enabling consumer self-sufficiency, fails to ameliorate these problems. The methodology identifies a grid’s susceptibility to disruption resulting from its network structure and modes of operation.
Significant role of spin-triplet state for exciton dissociation in organic solids
Authors: Yamanaka Takahiko , Nakanotani Hajime , Adachi Chihaya
Published: March 2022

Clarification of the role of the spin state that initiates exciton dissociation is critical to attaining a fundamental understanding of the mechanism of organic photovoltaics. Although an excited spin-triplet state with an energy lower than that of excited spin-singlet state is disadvantageous in exciton dissociation, a small electron exchange integral results in small singlet-triplet energy splitting in some material systems. This energy splitting leads to a nearly isoenergetic alignment of both excited states, raising a question about the role of excited spin states in exciton dissociation. Herein, we show that the spin-triplet rather than the spin-singlet plays a critical role in the exciton dissociation that leads to the formation of free carriers. This result indicates that the spin-triplet inherently acts as an intermediate, leading to exciton dissociation. Thus, our demonstration provides a fundamental understanding of the role of excited spin states of organic molecular systems in photoinduced charge-carrier generation.
Likelihood-based Mendelian randomization analysis with automated instrument selection and horizontal pleiotropic modeling
Authors: Yuan Zhongshang , Liu Lu , Guo Ping , Yan Ran , Xue Fuzhong , Zhou Xiang
Published: March 2022

Mendelian randomization (MR) is a common tool for identifying causal risk factors underlying diseases. Here, we present a method, MR with automated instrument determination (MRAID), for effective MR analysis. MRAID borrows ideas from fine-mapping analysis to model an initial set of candidate single-nucleotide polymorphisms that are in potentially high linkage disequilibrium with each other and automatically selects among them the suitable instruments for causal inference. MRAID also explicitly models both uncorrelated and correlated horizontal pleiotropic effects that are widespread for complex trait analysis. MRAID achieves both tasks through a joint likelihood framework and relies on a scalable sampling–based algorithm to compute calibrated
P
values. Comprehensive and realistic simulations show that MRAID can provide calibrated type I error control and reduce false positives while being more powerful than existing approaches. We illustrate the benefits of MRAID for an MR screening analysis across 645 trait pairs in U.K. Biobank, identifying multiple lifestyle causal risk factors of cardiovascular disease–related traits.
Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors
Authors: Nash Amanda M. , Jarvis Maria I. , Aghlara-Fotovat Samira , Mukherjee Sudip , Hernandez Andrea , Hecht Andrew D. , Rios Peter D. , Ghani Sofia , Joshi Ira , Isa Douglas , Cui Yufei , Nouraein Shirin , Lee Jared Z. , Xu Chunyu , Zhang David Y. , Sheth Rahul A. , Peng Weiyi , Oberholzer Jose , Igoshin Oleg A. , Jazaeri Amir A. , Veiseh Omid
Published: March 2022

Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)–producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.
Mitochondria in cone photoreceptors act as microlenses to enhance photon delivery and confer directional sensitivity to light
Authors: Ball John M. , Chen Shan , Li Wei
Published: March 2022

Mammalian photoreceptors aggregate numerous mitochondria, organelles chiefly for energy production, in the ellipsoid region immediately adjacent to the light-sensitive outer segment to support the high metabolic demands of phototransduction. However, these complex, lipid-rich organelles are also poised to affect light passage into the outer segment. Here, we show, via live imaging and simulations, that despite this risk of light scattering or absorption, these tightly packed mitochondria “focus” light for entry into the outer segment and that mitochondrial remodeling affects such light concentration. This “microlens”-like feature of cone mitochondria delivers light with an angular dependence akin to the Stiles-Crawford effect (SCE), providing a simple explanation for this essential visual phenomenon that improves resolution. This new insight into the optical role of mitochondria is relevant for the interpretation of clinical ophthalmological imaging, lending support for the use of SCE as an early diagnostic tool in retinal disease.
A carcinoembryonic antigen-specific cell therapy selectively targets tumor cells with HLA loss of heterozygosity in vitro and in vivo
Authors: Sandberg Mark L. , Wang Xueyin , Martin Aaron D. , Nampe Daniel P. , Gabrelow Grant B. , Li Chuck Z. , McElvain Michele E. , Lee Wen-Hua , Shafaattalab Sanam , Martire Sara , Fisher Fernando A. , Ando Yuta , Liu Edwin , Ju David , Wong Lu Min , Xu Han , Kamb Alexander
Published: March 2022

The
CEACAM5
gene product [carcinoembryonic antigen (CEA)] is an attractive target for colorectal cancer because of its high expression in virtually all colorectal tumors and limited expression in most healthy adult tissues. However, highly active CEA-directed investigational therapeutics have been reported to be toxic, causing severe colitis because CEA is expressed on normal gut epithelial cells. Here, we developed a strategy to address this toxicity problem: the Tmod dual-signal integrator. CEA Tmod cells use two receptors: a chimeric antigen receptor (CAR) activated by CEA and a leukocyte Ig-like receptor 1 (LIR-1)–based inhibitory receptor triggered by human leukocyte antigen (HLA)-A*02. CEA Tmod cells exploit instances of HLA heterozygous gene loss in tumors to protect the patient from on-target, off-tumor toxicity. CEA Tmod cells potently killed CEA-expressing tumor cells in vitro and in vivo. But in contrast to a traditional CEA-specific T cell receptor transgenic T cell, Tmod cells were highly selective for tumor cells even when mixed with HLA-A*02–expressing cells. These data support further development of the CEA Tmod construct as a therapeutic candidate for colorectal cancer.
Whole-Genome Sequencing and
De Novo
Assembly of 67 Staphylococcus pseudintermedius Strains Isolated from the Skin of Healthy Dogs
Authors: Fàbregas Norma , Pérez Daniel , Viñes Joaquim , Fonticoba Rocío , Cuscó Anna , Migura-García Lourdes , Ferrer Lluís , Francino Olga
Published: March 2022

We have
de novo
assembled 67
Staphylococcus pseudintermedius
genomes, with median values of 2.6 Mbp size and 99.43% completeness, 2,386 coding sequences, 19 complete rRNAs, 59 tRNAs, and 4 noncoding RNAs. We released 51 single-contig complete genomes and 16 genomes with a circular main contig using Nanopore sequencing.
WHO Critical Priority Escherichia coli as One Health Challenge for a Post-Pandemic Scenario: Genomic Surveillance and Analysis of Current Trends in Brazil
Authors: Fuga Bruna , Sellera Fábio P. , Cerdeira Louise , Esposito Fernanda , Cardoso Brenda , Fontana Herrison , Moura Quézia , Cardenas-Arias Adriana , Sano Elder , Ribas Rosineide M. , Carvalho Albalúcia C. , Tognim Maria Cristina B. , de Morais Marcia Maria C. , Quaresma Ana Judith P. G. , Santana Ângela Patrícia , Reis Joice N. , Pilonetto Marcelo , Vespero Eliana Carolina , Bonelli Raquel R. , Cerqueira Aloysio M. F. , Sincero Thaís C. M. , Lincopan Nilton
Published: March 2022

A One Health approach for antimicrobial resistance must integrate whole-genome sequencing surveillance data of critical priority pathogens from human, animal and environmental sources to track hot spots and routes of transmission and developing effective prevention and control strategies. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we present genomic data of WHO critical priority carbapenemase-resistant, ESBL-producing, and/or colistin-resistant
Escherichia coli
strains isolated from humans and nonhuman sources in Brazil, a country with continental proportions and high levels of antimicrobial resistance.
Neisseria meningitidis Serogroup C Clonal Complex 10217 Outbreak in West Kpendjal Prefecture, Togo 2019
Authors: Feagins Alicia R. , Sadji Adodo Yao , Topaz Nadav , Itsko Mark , Halatoko Jacqueline Wemboo Afiwa , Dzoka Alessou , Labite Joseph , Kata Yao , Gomez Sylvain , Kossi Komlan , Assane Hamadi , Nikiema-Pessinaba Christelle , Novak Ryan , Marjuki Henju , Wang Xin
Published: March 2022

The recent emergence of an invasive NmC strain in Togo is an example of the changing bacterial meningitis epidemiology in the meningitis belt post-MACV. The current epidemiology includes the regional circulation of various non-NmA serogroups, which emphasizes the need for effective molecular surveillance, laboratory diagnosis, and a multivalent vaccine that is effective against all serogroups in circulation.
HopE and HopD Porin-Mediated Drug Influx Contributes to Intrinsic Antimicrobial Susceptibility and Inhibits Streptomycin Resistance Acquisition by Natural Transformation in Helicobacter pylori
Authors: Liu Yixin , Yang Feng , Wang Su , Chi Wenjing , Ding Li , Liu Tao , Zhu Feng , Ji Danian , Zhou Jun , Fang Yi , Zhang Jinghao , Xiang Ping , Zhang Yanmei , Zhao Hu
Published: March 2022

Helicobacter pylori
is constitutively competent for natural transformation (NT) and possesses an efficient system for homologous recombination, which could be utilized to study the NT-mediated horizontal gene transfer induced antibiotic resistance acquisition. Bacterial porins have drawn renewed attention because of their crucial role in antibiotic susceptibility.
Performance of dRAST on Prospective Clinical Blood Culture Samples in a Simulated Clinical Setting and on Multidrug-Resistant Bacteria
Authors: Wong Alicia Y. W. , Johnsson Alexander T. A. , Özenci Volkan
Published: March 2022

There is an utmost need for rapid antimicrobial susceptibility testing (AST) of bacteria causing bloodstream infections (BSI). The dRAST (QuantaMatrix Inc., Seoul) is a rapid AST method that can be performed directly from positive blood cultures.
Soil Aggregates and Fertilizer Treatments Drive Bacterial Interactions via Interspecies Niche Overlap
Authors: Xiong Xiang , Liao Hao , Xing Yanfang , Han Xukun , Wang Wanle , Wan Wenjie , Huang Qiaoyun , Chen Wenli
Published: March 2022

Despite that the influence of soil structure and fertilizer treatments on the bacterial community has been widely studied, how they drive interspecies interactions has not been largely explored. Connectance and nestedness were significantly correlated with bacterial interactions, but no differences were found in different soil aggregates and fertilizer treatments.
Orbital forcing of late Early Devonian storm events on a mixed carbonate-siliciclastic shelf, Longmenshan area, Sichuan Province, China
Authors: Li Fengjie , Chen Zheng’an , Ogg James G , Li Zuoqiang , Ma Xiaokang , Lai Xuelian
Published: March 2022

The Yangmaba Formation of latest Early Devonian age in the Longmenshan area of Sichuan Province, China, is a shelfal facies that consists of four types of carbonate-siliciclastic deposits: clay-rich, siliciclastic sand-rich, carbonate-dominated, and hybrid mixed. Storm deposits vary in their thickness, composition, and abundance-per-meter within these mixed carbonate-siliciclastic deposits. Meter-scale statistics of the relative storm frequency (events-per-meter) and magnitude (bed thickness) were compiled in two coeval sections through each of the hybrid facies in the lower Yangmaba Formation, which spans approximately the entire conodont Polygnathus patulus Zone of the uppermost Emsian Stage. Low-pass filtering, spectral analysis, and Acycle software interpretation of these tempestite statistics yield 3.5 main oscillations in each section, with an average wavelength of ~23 m. These long-wavelength trends are semi-coincident with interpreted long-term variations in sea level, where shallower depths allowed a greater influence by storms. Superimposed on the long-wavelength cycles are medium-wavelength cycles of 5.5–6.3 m. The estimated ~1.5 m.y. time-span of this conodont zone of the lower Yangmaba Formation and the approximate 1:4 ratios of these wavelengths indicate that frequency and intensity of major storms and the recording of tempestites in the sedimentary record were modulated by ~100- and 95-k.y.-short-eccentricity orbital-climate oscillations superimposed on a main 405-k.y.-long-eccentricity cycle. These eccentricity climate cycles governed storm intensity and regional sea level on this margin of the tropical Yangtze Platform of South China.
Congenital long QT syndrome presenting as unexplained bradycardia
Authors: Ataíde Silva Rita , R Sousa Ana , de Carvalho Maria Salomé Leal , Anjos Rui
Published: March 2022

Congenital long QT syndrome (LQTS) is a genetically autosomal heterogeneous disorder of the ion channels and causes about 10% of sudden death infant syndrome in newborns. Its estimated prevalence is approximately 1 in 2500, probably underestimated because of its clinical heterogenicity. Few cases of neonatal LQTS have been reported. In 4% of them, life-threatening arrhythmic events can be the first manifestation of LQTS. The authors report two cases of neonatal LQTS with heterogeneous genetic mutations. Both manifested by bradycardia, one since fetal life. One case had serious arrhythmias during beta blocker therapeutic establishment needing a pacemaker implantation. Genetic mutations found were not the most frequently described in association with neonatal bradycardia, thus the importance of this report. Presentation with bradycardia is relatively frequent in neonatal period, thus LQTS should be actively investigated in neonates with unexplained bradycardia. Beta blocker therapy reduces QTc and avoids arrhythmic events and sudden death.
Apert syndrome: an informative long-term dentofacial outcome
Authors: Fowler Peter , Hallang Shirleen , Snape Leslie
Published: March 2022

The management of patients with Apert syndrome (AS) is complex and reflects the multisystem disease as a result of premature fusion of cranial vault, cranial base and midface sutures as well as extremity anomalies characterised by syndactyly. Early cranial sutural fusion results in craniocerebral disproportion which can lead to crisis surgical intervention due to raised intracranial pressure, ophthalmic and compromised airway concerns. Childhood inventions are often determined by psychosocial concerns and adult surgical interventions are often determined by cosmetic concerns. Treatments are provided by many different specialists within multidisciplinary teams (MDT). The treatment pathway extends from birth well into adulthood and is often associated with a heavy burden of care. Due to the extensive nature of the interaction with these patients MDT members have opportunities to provide enhanced patient-centred care and support.

This case report provides an overview of the current knowledge of the aetiology of AS, illustrates the pathway of surgical and non-surgical management of AS and provides a long-term review of the dentofacial treatment outcomes.

By having a better understanding of the impact of AS and treatment provided, MDT members can not only provide improved clinical treatment but also offer improved patient experiences for those with craniofacial anomalies, in particular, an increased awareness of the psychosocial challenges they endure.
Multidisciplinary approach to anti-MDA5 antibody-positive dermatomyositis associated with rapidly progressive interstitial lung disease
Authors: Witkowska Anna Barbara , Cowley Sharon , Dempsey Philip , Stack John
Published: March 2022

A man in his 40s was referred to our centre with rapidly progressive interstitial lung disease for lung transplant evaluation. Three months prior to his presentation he had developed periorbital oedema and discolouration, papules over the dorsal aspect of his metacarpophalangeal (MCP) joints and mucocutaneous ulcerations over the dorsum and palmar aspects of his MCPs. He had also been experiencing progressive shortness of breath. Based on the characteristic appearance of the cutaneous lesions, lack of muscle weakness on clinical examination, rapid progression of the interstitial lung disease together with presence of melanoma differentiation-associated gene 5 (MDA5) antibodies a diagnosis of anti-MDA5 dermatomyositis was made. Prompt treatment was initiated with aggressive combined immunomodulatory therapy that resulted in significant improvement in symptoms.
Enterolith in Roux limb causing extrahepatic biliary obstruction in a patient with a hepaticojejunostomy: case report and relevant literature review
Authors: Kumar Vipan , Mulpuri Venu Bhargava , Gupta Pankaj , Gupta Vikas
Published: March 2022

Enterolith in the Roux limb of hepaticojejunostomy causing jaundice is a rare occurrence. A 40-year-old woman had an extrahepatic biliary obstruction and cholangitis 13 years after the Roux-en-Y repair of postcholecystectomy benign biliary stricture. On evaluation, an enterolith was obstructing the Roux limb, which was successfully managed surgically.
Anaplastic large cell lymphoma, ALK-negative of the breast diagnosed a short time after removal of breast implant in a patient with breast carcinoma: diagnostic and therapeutic considerations
Authors: Riis Margit , Csanaky György , Lehne Gustav , Tangerud Aase
Published: March 2022

A case of mass-forming breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) with onset a short time after explanation of the cosmetic prosthesis is reported. The cause of implant removal was carcinoma diagnosed in the ipsilateral breast. The rarity of an almost synchronous manifestation of BIA-ALCL and breast carcinoma and the diagnostic challenges of mass-forming BIA-ALCL in a previously operated breast substantiate this report. The clinical course, diagnostic workup and therapeutic considerations are presented and discussed in detail. This case shows that a diagnosis of BIA-ALCL must always be considered even without a prosthesis in place in patients with a long history of textured implants.
Rare cause of left eye floaters and blurred vision in an immunocompromised patient: acute retinal necrosis (ARN)
Authors: Dong Xia , Wee Cleo , Xu Dan , Wan Pengxia
Published: March 2022

Acute retinal necrosis (ARN) is a clinical syndrome featuring severe vitritis and occlusive vasculitis characterised by full thickness necrotising retinitis. ARN is usually caused by an acute infection by either varicella zoster virus or herpes simplex virus, rarely cytomegalovirus (CMV). ARN often occurs in healthy adults; occasionally affecting immunocompromised patients with poor prognosis including significant visual loss and detachment of the atrophic retina regardless of antiviral treatment. We presented a man in his early 30s with a history of left eye floaters and blurred vision. He was diagnosed with T-cell acute lymphoblastic leukaemia 1 year ago and treated with chemotherapy and allogenic haematopoietic stem cell transplant 5 months ago. His clinical diagnosis was left eye ARN caused by acute viral infection with CMV being the most likely cause, which is rarely seen in immunocompromised patients. Our case highlighted a diagnostic and therapeutic challenge in the absence of guideline or evidence-based literature to follow.
Vitamin D levels in Portuguese military personnel
Authors: Henriques Moisés , Soares P , Sacadura-Leite E
Published: March 2022

Introduction

In Portugal, most adults have inadequate levels of vitamin D. Active duty military personnel need to be always ready for duty, perform tasks in specific contexts and overcome high physical and mental demands, which raises the relevance of knowing their vitamin D levels. This study aims to characterise vitamin D levels of Portuguese active duty military personnel and evaluate the effect of military status on the prevalence of vitamin D sufficiency, adjusted for season of the year, age and gender.

Methods

A retrospective cross-sectional study, based on vitamin D measurements carried out at the Armed Forces Hospital between 2014 and 2020, was fulfilled including the variables age, gender, vitamin D level and dosing date for military personnel and civilians. Comparison of proportions test and the generalised linear regression model were used for data analysis with a significance level of 5%.

Results

Out of 2782 subjects, 62.7% were military personnel. Mean±SD level of vitamin D was 24.5±10.6 ng/mL and 23.7±11.5 ng/mL in military personnel and civilians, respectively. In the military personnel, the prevalence of vitamin D sufficiency, insufficiency and deficiency was, respectively, 25.2%, 40.1% and 34.6%. Prevalence of vitamin D sufficiency was similar in the civilians cohort and, also, between Armed Forces branches. Military status had no effect on the prevalence of vitamin D sufficiency, especially after adjustments.

Conclusions

We present data on vitamin D levels of Portuguese active duty military personnel. Our results found that military personnel are no more at risk of vitamin D inadequacy than civilians, but only a quarter of active duty military personnel had vitamin D sufficiency. Therefore, they can benefit from vitamin D levels assessment towards vitamin D levels optimisation. Further studies are still needed, especially among military personnel with higher risk of vitamin D deficiency.