bluuebunny/crossref_metadata_2025 huggingface dataset:
High-throughput Screening in Combination With a Cohort Study for Iodothyronine Deiodinases
Authors: Yamauchi Ichiro , Sakane Yoriko , Okuno Yukiko , Sugawa Taku , Hakata Takuro , Fujita Haruka , Okamoto Kentaro , Taura Daisuke , Yamashita Takafumi , Hirota Keisho , Ueda Yohei , Fujii Toshihito , Yasoda Akihiro , Inagaki Nobuya
Published: June 2022

Regulatory mechanisms of iodothyronine deiodinases (DIOs) require further elucidation, and conventional methods for evaluating DIOs are unsuitable for high-throughput screening (HTS). Here we explored factors of transcriptional regulation of 3 types of DIOs (DIO1, DIO2, and DIO3) from a chemical library using our designed HTS. We constructed HTS based on a promoter assay and performed a screen of 2480 bioactive compounds. For compounds that were clinically approved, we validated hit compounds through a retrospective cohort study in our department that evaluated changes in thyroid function in patients using the compounds as drug therapy. Furthermore, we verified the involvement of DIOs using mice treated with the compounds. Of the hit compounds, 6 and 7 compounds transcriptionally up- and downregulated DIO1, respectively; 34 transcriptionally upregulated DIO2; and 5 and 2 compounds transcriptionally up- and downregulated DIO3, respectively. The cohort study clarified the clinical effects of some hit compounds: ritodrine increased free triiodothyronine (fT3)/free thyroxine (fT4) ratio and decreased serum thyroid-stimulating hormone (TSH) levels, tadalafil increased serum fT3 levels, and tyrosine kinase inhibitors (TKIs) decreased serum fT3 and fT4 levels and increased serum TSH levels. Following in vivo experiments using treated mice, consistent results were observed in ritodrine, which upregulated DIO2 in the thyroid gland. In conclusion, we completed HTS for DIOs and obtained attractive hit compounds. Our cohort study revealed the clinical significance of ritodrine, sildenafil, and TKIs. We hope our unique method will contribute to analyzing various targets and lists of hit compounds will promote understanding of DIOs.
Whole Body, Whole Life, Whole Family: Patients’ Perspectives on X-Linked Hypophosphatemia
Authors: Hamilton Amber A , Faitos Susan , Jones Gin , Kinsley Athina , Gupta Rupal Naik , Lewiecki E Michael
Published: June 2022

The rare genetic disorder X-linked hypophosphatemia (XLH) is often exclusively considered to impact children, and, as such, adult patients with XLH may receive inadequate care because their symptoms are not associated with XLH. However, studies have shown that XLH has long-term adverse health consequences that continue throughout adulthood requiring comprehensive lifelong care. Indeed, XLH impacts patients’ whole body, whole life, and whole family. XLH does not just affect the bones; symptoms are chronic and progressive, worsening throughout adulthood, and the burden of XLH overflows into the lives of a patient’s family, friends, peers, and colleagues. To ensure early recognition, comprehensive care, and adequate management of XLH, there are key steps that clinicians can incorporate into their daily practice. These include education, a multidisciplinary approach, open communication, and support. Clinician education on rare disorders such as XLH is critical, and healthcare professionals (HCPs) should ensure that patients and their caregivers have access to XLH-related information. As a whole-body disorder, XLH requires a coordinated approach to treatment across specialties. Frequent open communication among members of the healthcare team is needed to increase HCPs’ knowledge about XLH, and open communication must extend to the patient as well to ensure the patient’s concerns and needs are addressed and treatment is tailored to their specific individual needs. Multiple networks of support, including social and psychological support, should be offered to patients and their families. A basic understanding that XLH affects patients’ whole bodies, whole lives, and whole families is the first step toward accomplishing improved patient care.
Fresh Fruit and Rotten Railroads
Authors: Barnes Bryant K.
Published: June 2022

Georgia fruit growers embodied the intelligent, business-minded mentality about which New South boosters preached. Rather than stubbornly adding to the already glutted cotton markets, these modern farmers diversified. In supplying urban markets with fruit and truck, growers drew the attention of northern capital southward. Queen Peach and her cousins would supplant King Cotton and bring prosperity to the prostrate South. Yet it was with the New South's critics that many growers allied themselves in the 1890s. Despite epitomizing scientific agriculture and virtuous industry, Georgia growers asserted the near impossibility of squeezing profits from fruit. Railroads, they argued, hindered the promised progress and liberation through extortionate freight rates. Consequently, growers became leaders of Georgia's Populist revolt. Their story challenges notions of Populism as backward-looking while revealing the inefficiencies, failures, and precarities of corporate capitalism exemplified by southern railroads. Moreover, it demonstrates the Populists' distinct threat to the rising corporate order.
From 1990 to 2020
Authors: Newfield Christopher
Published: June 2022

Thinking about the past thirty years can help readers get a sense of the scale of changes that are possible during the thirty years to come. In 1990, the Soviet Union and the Cold War were in place, computers were a niche business, and the world's leading advocates of deep neoliberalization, Ronald Reagan and Margaret Thatcher, were out of power. Not many years later, the Cold War had been replaced by a “Global War on Terror,” computers had morphed into a global techno-economic system with names like platform capitalism or surveillance capitalism, and neoliberalization not only outlived these dominant advocates but spread around the world. Simultaneously, work, including the work of university graduates, became increasingly precarious. Racial equality did not come to pass, nationally or globally, and yet even its prospect produced a rising backlash. The post–Cold War “peace dividend” was replaced by continuous local and regional wars. In the past thirty years, the United States in particular became post–middle class, post–civil rights, and postdemocratic. Future universities will need to confront all three legacies if they are to transform themselves.
Brazilian Universities under Attack
Authors: Arantes Pedro Fiori
Published: June 2022

Brazil has around half of Latin America's twenty-five best-ranked universities, and all of them are public. Most Brazilian public universities are also socially embedded, building knowledge in dialogue with communities, and are involved in defending human rights, social justice, and environmental sustainability. They are a fundamental part of the Brazilian biopolitical pact that has prevailed in recent decades. Brazil's new, openly authoritarian government has chosen this public university system as a central target, pursuing two courses of action: one a radical neoliberal agenda and the other an ideological war on the production of critical, social, and scientific knowledge. For this regime and its necropolitical bias, public universities are no longer necessary institutions. Nevertheless, despite all the attacks against them, universities have acted as important institutions in Brazil during the COVID-19 pandemic, defending life and human rights.
Wildcat Imaginaries
Authors: Gilich Yulia , Boardman Tony
Published: June 2022

The demand for a Cost of Living Adjustment (COLA), made by graduate students at the University of California, Santa Cruz (UCSC), culminated in the wildcat strikes of 2019–20 across the University of California system. Graduate students made a seemingly impossible request of the University of California as it currently operates. The impossibility is not financial: a 60 percent increase in wages, in keeping with the COLA demand, is not unreasonable or impossible but remains the bare minimum to bring graduate students out of an intolerable rent burden. The impossibility of the demand therefore resides in the system's resistance to conceiving of students as “workers.” By insisting on graduate students' status as workers, the COLA struggle implicates the university in the production of low-waged and unwaged academic labor. This struggle demonstrates a commonality between students and a whole class of low-waged and precarious workers at the university that includes university staff, lecturers, and service workers. Extreme precarity that triggered the wildcat strike was intensified by police repression of the picket and the unfolding of the COVID-19 pandemic. As they grapple with the questions of university abolition, the authors of this article examine the structural violences of universities at large, while being attentive to the particularities of the UCSC wildcat strike. The authors draw on the wildcat imaginaries that emerged, in both inchoate and more developed formations, during the strike and offered a glimpse of a possible abolitionist future.
University Rankings
Authors: Gavroglu Kostas
Published: June 2022

The ranking systems for universities aim at the quantification of all aspects of university life. For many decades, universities prided themselves on the differences among them. Rankings reduced discussions about the qualitative differences among universities to discussions of numerical differences. Perhaps the closest one can get to drawing a road map of the present and future of universities is understanding the form and content of the rankings within the overall framework of the digital condition. The digital condition already forces the adoption of new ethical modes, restructures working time, imposes styles of reading, affects teaching, and dictates new research practices. But above all, the rearticulations of democracy due to the digital condition will mark the new state of the universities. And such a prospect can perhaps be defined within Bill Sharpe's three horizons framework.
Imagination and the Future University
Authors: Facer Keri
Published: June 2022

This essay argues that thinking about university futures requires not only practices of critique and desire, but practices of rigorous and reflexive imagination. Building on Bill Sharpe's three horizons framework, it argues that debates about university futures are dominated by horizon 1 thinking (critique of the current situation) and horizon 3 thinking (normative aspirations toward desirable futures) but that there is limited exploration of horizon 2 (the emerging possibilities that may create radical disruption). The article draws on futures and anticipation studies, in particular Ziauddin Sardar and John Sweeney's “postnormal menagerie,” to model a set of imaginative inquiries into the blind spots, blank spots, and different forms of ignorance through which highly divergent university futures might be explored. It concludes by proposing two scenarios for university futures—the “Campus of the Sky” and the “Pirate University”—as sites of generative experimentation and further research, and with a call for a radical diversification of participation in dialogues about the future of the university.
Simulation and nurse-mentoring in a statewide nurse mentoring program in Bihar, India: diagnosis of postpartum hemorrhage and intrapartum asphyxia
Authors: Ghosh Rakesh , Cohen Susanna , Spindler Hilary , Vincent Divya , Sterling Mona , Das Aritra , Gore Aboli , Mahapatra Tanmay , Walker Dilys
Published: June 2022

Background: Mentoring programs that include simulation, bedside

mentoring, and didactic components are becoming increasingly

popular to improve quality. These programs are designed with little

evidence to inform the optimal composition of mentoring activities that

would yield the greatest impact on provider skills and patient

outcomes. We examined the association of number of maternal and

neonatal emergency simulations performed in trainings with the diagnosis of

postpartum hemorrhage (PPH) and intrapartum asphyxia in real

patients.

Methods: We used a prospective cohort and births were compared between- and within-facility over time.

Setting included 320 public

facilities in the state of Bihar, India May 2015 – 2017. The participants

were Deliveries and livebirths. The interventions carried out were

mobile nurse-mentoring program with simulations, teamwork and

communication activities, didactic teaching, demonstrations of clinical

procedures and bedside mentoring including conducting deliveries.

Nurse mentor pairs visited each facility for one week, covering four

facilities over a four-week period, for seven to nine consecutive

months. The outcome measures were diagnosis of PPH and

intrapartum asphyxia.

Results: Relative to the bottom one-third facilities that performed the

fewest maternal simulations, facilities in the middle one-third group

diagnosed 26% (incidence rate ratio [IRR] = 1.26, 95% confidence

interval [CI]: 1.00, 1.59) more cases of PPH in real patients. Similarly,

facilities in the middle one-third group, diagnosed 25% (IRR = 1.25,

95% CI: 1.04, 1.50) more cases of intrapartum asphyxia relative to the

bottom third group that did the fewest neonatal simulations. Facilities

in the top one-third group (i.e., performed the most simulations) did

not have a significant difference in diagnosis relative the bottom one-third group.

Conclusions: Findings suggest a complex relationship between

performing simulations and opportunities for direct practice with

patients, and there may be an optimal balance in performing the two

that would maximize diagnosis of PPH and intrapartum asphyxia.
Recognising the deterioration of patients in acute care wards: a qualitative study
Authors: Beane Abi , Wijesiriwardana Wageesha , Pell Christopher , Dullewe N. P. , Sujeewa J. A. , Rathnayake R. M. Dhanapala , Jayasinghe Saroj , Dondorp Arjen M. , Schultsz Constance , Haniffa Rashan
Published: June 2022

Background: Infrastructure, equipment and staff constraints are often cited as barriers to the recognition and rescue of deteriorating patients in resource-limited settings. The impact of health-system organisation, decision-making and organisational culture on recognition of deterioration is however poorly understood. This study explores how health care providers recognise deterioration of patients in acute care in Sri Lanka.

Methods: In-depth interviews exploring decision making and care processes related to recognition of deterioration, were conducted with a purposive sample of 23 health care workers recruited from ten wards at a district hospital in Sri Lanka. Interviews were audio-recorded, transcribed and coded thematically, line-by-line, using a general inductive approach.

Results: A legacy of initial assessment on admission and inimical organisational culture undermined recognition of deteriorating patients in hospital. Informal triaging at the time of ward admission resulted in patients presenting with red-flag diagnoses and vital sign derangement requiring resuscitation being categorised as "bad". The legacy of this categorisation was a series of decision-making biases anchored in the initial assessment, which remained with the patient throughout their stay. Management for patients categorised as “bad” was prioritised by healthcare workers coupled with a sense of fatalism regarding adverse outcomes. Health care workers were reluctant to deviate from the original plan of care despite changes in patient condition (continuation bias). Organisational culture - vertical hierarchy, siloed working and a reluctance to accept responsibility- resulted in omissions which undermined recognition of deterioration. Fear of blame was a barrier to learning from adverse events.

Conclusions: The legacy of admission assessment and hospital organisational culture undermined recognition of deterioration. Opportunities for improving recognition of deterioration in this setting may include establishing formal triage and medical emergency teams to facilitate timely recognition and escalation.
Efficacy and safety of atropine to control childhood myopia progression
Authors: Lewkowicz Martyna , Nowakowska Katarzyna , Pawlina Mateusz , Raksa Karolina , Ziętara Karolina , Kozioł Magdalena
Published: June 2022

Introduction: Nearsightedness is one of the most common eye defects in people all over the world. If left untreated, it leads to a number of serious eye complications that can result in irreversible loss of vision. It is estimated that by 2050. Half of humanity will be burdened with this disadvantage, so it has become a priority to try to find ways to prevent and treat myopia, among which the administration of atropine drops is very effective.

Aim of the study: The aim of this study is to evaluate the safety and efficacy of atropine in controlling the progression of myopia and to investigate the relationship between the dose of atropine and the effectiveness of controlling the progression of myopia.

Material and methods: The PubMed and Google Scholar databases were used to review the literature.

Results: Eye drops with 1% atropine showed the greatest efficacy in the control of myopia. However, their use was limited due to the occurrence of side effects such as impaired accommodation and photophobia. In the ATOM 2 study, which investigated the use of atropine in a variety of concentrations, it was found that 0.01% is the optimal concentration with good efficacy and minimal side effects. One of the breakthroughs was the LAMP study using atropine at a concentration of 0.05%, 0.025%, 0.01% in eye drops. This study provided evidence for the first time that low-concentration atropine is effective compared with placebo in myopia. In addition, both efficacy and side effects followed a concentration-dependent response ranging from 0.01% to 0.05% of atropine. Among them, 0.05% of atropine was the optimal concentration to achieve the best efficacy and safety profile.

Conclusion: Low concentration of atropine is effective in the control of myopia. Its widespread use can help prevent the progression of myopia. However, further investigation of the rebound phenomenon and a long term, individualized approach to treatment are warranted.
Effectiveness of physiotherapeutic techniques in urinary incontinence: a review of the literature
Authors: Wójcik Agata , Lamch Magdalena , Błasik Natalia , Jabłońska Monika , Tomys Julia , Strugała Urszula , Kędziora–Kornatowska Kornelia
Published: June 2022

Introduction and purpose : Urinary incontinence is a common condition characterized by involuntary urine leakage from urethra. It particularly affects elderly women and is a serious medical, social and economic problem. As a result of recently observed population ageing, the incidence of this anomaly is expected to rise. Due to multifactorial etiology, several types of incontinence are distinguished. Proper diagnostic procedures lead to diagnosis confirmation and allow appropriate therapeutic intervention. Both conservative and surgical methods are used in management of urine incontinence. In addition to pharmacological therapy, physiotherapeutic methods have an important meaning in conservative approach. The aim of this article is a review presenting the results of recent studies on the effectiveness of physiotherapy procedures in treatment of various types of urine incontinence.
Description of the state of knowledge: In the study 33 articles which published physiotherapy techniques in 2004-2021 regarding the role of physiotherapeutic methods in the treatment of urinary incontinence were analyzed. The results of studies assessing the effectiveness of physiotherapy techniques (acupuncture, behavioral therapy, yoga, magnetic stimulation, pelvic floor muscle training, vaginal cones, vibration therapy, kinesiotheraphy techniques, stimulation) in reducing the severity of urinary incontinence symptoms and improving the quality of patients’ life were presented on the basis of analyzed literature.
Conclusions: Physiotherapy is an effective method of treatment of urinary incontinence and it supports other types of therapy. Therapy should be interdisciplinary approached and the choice of physiotherapeutic methods should be dependent on the individual needs of the patient.
Anchored Inferential Learning: Platform-Specific Uncertainty, Venture Capital Investments by the Platform Owner, and the Impact on Complementors
Authors: van Angeren Joey , Karunakaran Arvind
Published: June 2022

Platform owners increasingly make corporate venture capital investments in complementors (e.g., app developers) to stimulate value creation, a practice we refer to as platform venture capital (PVC). Interested in the implications of PVC for other complementors, we investigate how PVC investments affect their product introduction and withdrawal decisions. Given that complementors confront platform-specific uncertainty concerning the strategic directions of the platform, which is asymmetrically set by the platform owner, we theorize that complementors leverage PVC investments as devices for anchored inferential learning. That is, because PVC investments are costly, visible, and consequential, complementors will infer them as credible indicators of the platform’s future focus. Consequently, we predict that complementors will seek out, and stick around, product categories of PVC investees. We further anticipate that these inclinations are weaker for complementors with greater platform ecosystem experience that place more emphasis on knowledge acquired via experiential learning, and stronger for complementors that center their business exclusively on the platform and therefore rely strongly on PVC to navigate platform-specific uncertainty. We provide quantitative evidence from the context of the Salesforce platform. Moreover, we draw on qualitative data from this context to unpack why complementors interpret PVC investments as a credible signal concerning the strategic direction of the platform. We highlight that complementors consider PVC as a form of middle-ground platform governance, where the platform owner is perceived as being committed to stimulating value creation in the platform ecosystem, while also inducing complementors to commit their efforts to the platform ecosystem.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2022.1607 .
Theoretical determination of biaxial anisotropy suitable for reducing incident angle dependence of a high-efficiency polarization grating
Authors: Momosaki Ryusei , Sakamoto Moritsugu , Noda Kohei , Tamayama Yasuhiro , Sasaki Tomoyuki , Unuma Takeya , Sakai Takeya , Hattori Yukitoshi , Kawatsuki Nobuhiro , Ono Hiroshi
Published: June 2022

A theoretical framework for determining biaxial anisotropy suitable for
reducing the incident angle dependence of a polarization grating is
proposed. The principal refractive indices are uniquely given by
quantifying the biaxial anisotropy through the

N
z

coefficient. The numerical analysis
based on the finite-difference time-domain method reveals that the
incident angle dependences of the diffraction efficiency and the
polarization ellipticity of the diffracted light are significantly
reduced when

N
z
=

0.5

. This result is expected to
contribute to the design of polarization diffractive optical elements
and the development of anisotropic materials and structures.
Enhanced prediction performance of a time-delay reservoir computing system based on a VCSEL by dual-training method
Authors: Gu Bi Ling , Xiang Shui Ying , Guo Xing Xing , Zheng Dian Zhuang , Hao Yue
Published: June 2022

In this paper, a new dual-training method for a time-delay reservoir computing (RC) system based on a single vertical-cavity surface-emitting laser (VCSEL) is proposed and demonstrated experimentally for the first time. The prediction performance of the RC system by using the dual-training method has been experimentally and numerically investigated. Here, the dual-training method is defined as performing a further RC based on the difference between the target value and the predicted value of the traditional single training. It is found that enhanced prediction performance of the RC system can be obtained by employing the dual-training method, compared to the traditional single training method. More specifically, the NMSE values of the RC system with the dual-training method applied can be improved to 760% compared with the single training method in experiments. Besides, the effects of injection power, bias currents, feedback strength, and frequency detuning are also considered. The proposed dual-training method is of great significance to the performance enhancement of the RC and has an important promotion effect on the application of the RC in the future.
Axial accuracy in localization microscopy with 3D point spread function engineering
Authors: Siemons Marijn E. , Kapitein Lukas C. , Stallinga Sjoerd
Published: June 2022

Single-molecule localization microscopy has developed into a widely used technique to overcome the diffraction limit and enables 3D localization of single-emitters with nanometer precision. A widely used method to enable 3D encoding is to use a cylindrical lens or a phase mask to engineer the point spread function (PSF). The performance of these PSFs is often assessed by comparing the precision they achieve, ignoring accuracy. Nonetheless, accurate localization is required in many applications, such as multi-plane imaging, measuring and modelling of physical processes based on volumetric data, and 3D particle averaging. However, there are PSF model mismatches in the localization schemes due to how reference PSFs are obtained, look-up-tables are created, or spots are fitted. Currently there is little insight in how these model mismatches give rise to systematic axial localization errors, how large these errors are, and how to mitigate them. In this theoretical and simulation work we use a vector PSF model, which incorporates super-critical angle fluorescence (SAF) and the appropriate aplanatic correction factor, to analyze the errors in z-localization. We introduce theory for defining the focal plane in SAF conditions and analyze the predicted axial errors for an astigmatic PSF, double-helix PSF, and saddle-point PSF. These simulations indicate that the absolute axial biases can be as large as 140 nm, 250 nm, and 120 nm for the astigmatic, saddle-point, and double-helix PSF respectively, with relative errors of more than 50%. Finally, we discuss potential experimental methods to verify these findings and propose a workflow to mitigate these effects.
Correcting projector lens distortion in real time with a scale-offset model for structured light illumination
Authors: Zhang Geyou , Xu Bin , Lau Daniel L. , Zhu Ce , Liu Kai
Published: June 2022

In fringe projection profilometry, inevitable distortion of optical lenses decreases phase accuracy and decreases the quality of 3D point clouds. For camera lens distortion, existing compensation methods include real time look-up tables derived from the related parameters of camera calibration. However, for projector lens distortion, so far, post-undistortion methods iteratively correcting lens distortion are relatively time-consuming while, despite avoiding iteration, pre-distortion methods are not suitable for binary fringe patterns. In this paper, we aim to achieve real-time phase correction for the projector by means of a scale-offset model that characterizes projector distortion by four correction parameters within a small-enough area, and thus we can speed up the post-undistortion by looking up tables. Experiments show that the proposed method can suppress the distortion error by a factor of 20 ×, i.e., the error of root mean square is less than 45 µm/0.7‰, while also proposed improving the computation speed by a factor of 50× over traditional iterative post-undistortion.
Watt-level femtosecond Tm-doped “mixed” sesquioxide ceramic laser in-band pumped by a Raman fiber laser at 1627 nm
Authors: Zhang Ning , Wang Zhanxin , Liu Shande , Jing Wei , Huang Hui , Huang Zixuan , Tian Kangzhen , Yang Zhiyong , Zhao Yongguang , Griebner Uwe , Petrov Valentin , Chen Weidong
Published: June 2022

We report on a semiconductor saturable absorber mirror mode-locked Tm:(Lu,Sc)2O3 ceramic laser in-band pumped by a Raman fiber laser at 1627 nm. The nonlinear refractive index (n2) of the Tm:(Lu,Sc)2O3 ceramic has been measured to be 4.66 × 10−20 m2/W at 2000 nm. An average output power up to 1.02 W at 2060 nm is achieved for transform-limited 280-fs pulses at a repetition rate of 86.5 MHz, giving an optical efficiency with respect to the absorbed pump power of 36.4%. Pulses as short as 66 fs at 2076 nm are produced at the expense of output power (0.3 W), corresponding to a spectral bandwidth of 69 nm. The present work reveals the potential of Tm3+-doped sesquioxide transparent ceramics for power scaling of femtosecond mode-locked bulk lasers emitting in the 2-µm spectral range.
Inverse design of coupled subwavelength dielectric resonators with targeted eigenfrequency and Q factor utilizing deep learning
Authors: Pan Tuqiang , Ye Jianwei , Zhang Zhanyuan , Xu Yi
Published: June 2022

Subwavelength all-dielectric resonators supporting Mie resonances are promising building blocks in nanophotonics. The coupling of dielectric resonators facilitates advanced shaping of Mie resonances. However, coupled dielectric resonators with anisotropic geometry can only be designed by time-consuming simulation utilizing parameter scanning, hampering their applications in nanophotonics. Herein, we propose and demonstrate that a combination of two fully connected networks can effectively design coupled dielectric resonators with targeted eigenfrequency and Q factor. Typical examples are given for validating the proposed network, where the normalized deviation rates of eigenfrequency and Q factor are 0.39% and 1.29%, respectively. The proposed neutral network might become a useful tool in designing coupled dielectric resonators and beyond.
Spatially multiplexed single-cavity dual-comb laser
Authors: Pupeikis J. , Willenberg B. , Camenzind S. L. , Benayad A. , Camy P. , Phillips C. R. , Keller U.
Published: June 2022

Single-cavity dual-comb lasers are a new class of ultrafast lasers that have a wide possible application space including pump–probe sampling, optical ranging, and gas absorption spectroscopy. However, to date, laser cavity multiplexing has usually come with a trade-off in laser performance or relative timing noise suppression. We present a method for multiplexing a single laser cavity to support a pair of noise-correlated modes. These modes share all intracavity components and take a near-common path, but do not overlap on any active elements. We implement the method with an 80-MHz laser delivering more than 2.4 W of average power per comb with sub-140-fs pulses. We reach sub-cycle relative timing jitter of 2.2 fs [20 Hz, 100 kHz]. With this multiplexing technique, we can implement slow feedback on the repetition rate difference

Δ

f

r
e
p

, enabling this quantity to be drift-free, have low jitter, and be adjustable—a key combination for practical applications that was lacking in prior single-cavity dual-comb systems.
Context-dependent reversal of odorant preference is driven by inversion of the response in a single sensory neuron type
Authors: Khan Munzareen , Hartmann Anna H. , O’Donnell Michael P. , Piccione Madeline , Pandey Anjali , Chao Pin-Hao , Dwyer Noelle D. , Bargmann Cornelia I. , Sengupta Piali
Published: June 2022

The valence and salience of individual odorants are modulated by an animal’s innate preferences, learned associations, and internal state, as well as by the context of odorant presentation. The mechanisms underlying context-dependent flexibility in odor valence are not fully understood. Here, we show that the behavioral response of Caenorhabditis elegans to bacterially produced medium-chain alcohols switches from attraction to avoidance when presented in the background of a subset of additional attractive chemicals. This context-dependent reversal of odorant preference is driven by cell-autonomous inversion of the response to these alcohols in the single AWC olfactory neuron pair. We find that while medium-chain alcohols inhibit the AWC olfactory neurons to drive attraction, these alcohols instead activate AWC to promote avoidance when presented in the background of a second AWC-sensed odorant. We show that these opposing responses are driven via engagement of distinct odorant-directed signal transduction pathways within AWC. Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery.
Two types of critical cell density for mechanical elimination of abnormal cell clusters from epithelial tissue
Authors: Lee Sang-Woo , Morishita Yoshihiro
Published: June 2022

Recent technological advances in high-resolution imaging and artificial modulation of genetic functions at different times and regions have enabled direct observations of the formation and elimination of abnormal cell populations. A recent trend in cell competition research is the incorporation of cell mechanics. In different tissues and species, abnormal cells developing in epithelial tissues are mechanically eliminated by cell contraction via actomyosin accumulation at the interface between normal and abnormal cells. This mechanical cell elimination process has attracted attention as a potential universal defense mechanism. Here, we theoretically examined the conditions for mechanical elimination of growing abnormal cell populations. Simulations and mathematical analyses using a vertex dynamics model revealed two types of critical cell density associated with mechanical elimination of abnormal cell clusters. One is a subtype of homeostatic density, in which the frequencies of spontaneous mechanical cell elimination and proliferation are balanced, even if no explicit dependence of proliferation or apoptosis on the cell density is assumed. This density is related to the mechanical stability of a single cell. The other is density related to mechanical stability as a cell population under external pressure. Both density types are determined by tissue mechanical properties. In solid tissues, the former type is reached first as the intensity of interfacial contraction increases, and it functions as a critical density. On the other hand, the latter type becomes critical when tissues are highly fluid. The derived analytical solution explicitly reveals the dependence of critical contractile force and density on different parameters. We also found a negative correlation between the proliferation rate of abnormal cells and the likelihood of the abnormal cell population expanding by escaping elimination. This is counterintuitive because in the context of cell competition, fast-growing cell populations generally win. These findings provide new insight into, and interpretation of, the results from experimental studies.
Krüppel-like factor 15 integrated autophagy and gluconeogenesis to maintain glucose homeostasis under 20-hydroxyecdysone regulation
Authors: Wang Xiao-Pei , Huang Zhen , Li Yan-Li , Jin Ke-Yan , Dong Du-Juan , Wang Jin-Xing , Zhao Xiao-Fan
Published: June 2022

The regulation of glycometabolism homeostasis is vital to maintain health and development of animal and humans; however, the molecular mechanisms by which organisms regulate the glucose metabolism homeostasis from a feeding state switching to a non-feeding state are not fully understood. Using the holometabolous lepidopteran insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the steroid hormone 20-hydroxyecdysone (20E) upregulated the expression of transcription factor Krüppel-like factor (identified as Klf15) to promote macroautophagy/autophagy, apoptosis and gluconeogenesis during metamorphosis. 20E via its nuclear receptor EcR upregulated Klf15 transcription in the fat body during metamorphosis. Knockdown of Klf15 using RNA interference delayed pupation and repressed autophagy and apoptosis of larval fat body during metamorphosis. KLF15 promoted autophagic flux and transiting to apoptosis. KLF15 bound to the KLF binding site (KLF bs) in the promoter of Atg8 (autophagy-related gene 8/LC3) to upregulate Atg8 expression. Knockdown Atg8 reduced free fatty acids (FFAs), glycerol, free amino acids (FAAs) and glucose levels. However, knockdown of Klf15 accumulated FFAs, glycerol, and FAAs. Glycolysis was switched to gluconeogenesis, trehalose and glycogen synthesis were changed to degradation during metamorphosis, which were accompanied by the variation of the related genes expression. KLF15 upregulated phosphoenolpyruvate carboxykinase (Pepck) expression by binding to KLF bs in the Pepck promoter for gluconeogenesis, which utilised FFAs, glycerol, and FAAs directly or indirectly to increase glucose in the hemolymph. Taken together, 20E via KLF15 integrated autophagy and gluconeogenesis by promoting autophagy-related and gluconeogenesis-related genes expression.
Site-specific MCM sumoylation prevents genome rearrangements by controlling origin-bound MCM
Authors: Quan Yun , Zhang Qian-yi , Zhou Ann L. , Wang Yuhao , Cai Jiaxi , Gao Yong-qi , Zhou Huilin
Published: June 2022

Timely completion of eukaryotic genome duplication requires coordinated DNA replication initiation at multiple origins. Replication begins with the loading of the Mini-Chromosome Maintenance (MCM) complex, proceeds by the activation of the Cdc45-MCM-GINS (CMG) helicase, and ends with CMG removal after chromosomes are fully replicated. Post-translational modifications on the MCM and associated factors ensure an orderly transit of these steps. Although the mechanisms of CMG activation and removal are partially understood, regulated MCM loading is not, leaving an incomplete understanding of how DNA replication begins. Here we describe a site-specific modification of Mcm3 by the Small Ubiquitin-like MOdifier (SUMO). Mutations that prevent this modification reduce the MCM loaded at replication origins and lower CMG levels, resulting in impaired cell growth, delayed chromosomal replication, and the accumulation of gross chromosomal rearrangements (GCRs). These findings demonstrate the existence of a SUMO-dependent regulation of origin-bound MCM and show that this pathway is needed to prevent genome rearrangements.
Understanding leprosy reactions and the impact on the lives of people affected: An exploration in two leprosy endemic countries
Authors: Putri Annisa Ika , de Sabbata Kevin , Agusni Regitta I. , Alinda Medhi Denisa , Darlong Joydeepa , de Barros Barbara , Walker Stephen L. , Zweekhorst Marjolein B. M. , Peters Ruth M. H.
Published: June 2022

Background

Leprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions.

Methods/Principal findings

This qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4–6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization.

Conclusion

Leprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.
Recommendations of high-quality clinical practice guidelines related to the process of starting dialysis: A systematic review
Authors: Salas-Gama Karla , Onakpoya Igho J. , Coronado Daza Jorge , Perera Rafael , Heneghan Carl J.
Published: June 2022

Background

The optimal time for initiation of dialysis and which modality to choose as the starting therapy is currently unclear. This systematic review aimed to assess the recommendations across high-quality clinical practice guidelines (CPGs) related to the start of dialysis.

Methods

We systematically searched MEDLINE, EMBASE, Web of Science, LILACS, and databases of organisations that develop CPGs between September 2008 to August 2021 for CPGs that addressed recommendations on the timing of initiation of dialysis, selection of dialysis modality, and interventions to support the decision-making process to select a dialysis modality. We used the Appraisal of Guidelines for Research and Evaluation instrument to assess the methodological quality of the CPGs and included only high-quality CPGs. This study is registered in PROSPERO, number CRD42018110325.

Results

We included 12 high-quality CPGs. Six CPGs addressed recommendations related to the timing of initiating dialysis, and all agreed on starting dialysis in the presence of symptoms or signs. Six CPGs addressed recommendations related to the selection of modality but varied greatly in their content. Nine CPGs addressed recommendations related to interventions to support the decision-making process. Eight CPGs agreed on recommended educational programs that include information about dialysis options. One CPG considered using patient decision aids a strong recommendation.

Limitations

We could have missed potentially relevant guidelines since we limited our search to CPGs published from 2008, and we set up a cut-off point of 60% in domains of the rigour of development and editorial independence.

Conclusion

High-quality CPGs related to the process of starting dialysis were consistent in initiating dialysis in the presence of symptoms or signs and offering patients education at the point of decision-making. There was variability in how CPGs addressed the issue of dialysis modality selection. CPGs should improve strategies on putting recommendations into practice and the quality of evidence to aid decision-making for patients.

Registration

The protocol of this systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD CRD42018110325.

https://clinicaltrials.gov/ct2/show/CRD42018110325.
Ginseng of different ages is affected by the accumulation of heavy metals in ginseng soil
Authors: Yin Juxin , Zhuang Jianjian , Zhang Xin , Xu Chaojian , Lv Shaowu
Published: June 2022

Heavy-metal pollution has been established to affect ginseng quality. However, this effect is still unknown in ginseng of different ages, emphasizing the need to investigate the effects of heavy metals in soils on ginseng growth. Herein, we determined the content of heavy metals (Cu, Cd, Pb, Hg, and As) in ginseng of different ages (2 to 6-year-old) and the corresponding soil samples. Then, the total ginsenosides content of ginseng and rate-limiting enzyme (HMGR, SQE, CYP450) activity in the synthesis of ginsenosides were assessed. Results from 200 differently-aged Chinese ginseng showed that increased ginsenoside content in 3 to 5-year-old ginseng was paralleled by increased heavy metal element content in ginseng and its soil. The activity of rate-limiting enzymes increased in the first four years of ginseng growth and then exhibited a steady or downward trend. Further analysis suggested that heavy metal elements in soils could directly affect ginsenoside content. Moreover, we found that Cu significantly affected the rate-limiting enzyme CYP450 activity. Further principal component analysis and correlation analysis found that heavy metals could obviously inhibit ginseng growth during the 5th and 6th years. Heavy metal content in soils has huge prospects for predicting ginsenoside, Cu and As content in ginseng. This study provided support for ginseng cultivation, quality research and quality assessment.
Evaluation of the Amharic version of the London measure of unplanned pregnancy in Ethiopia
Authors: Olani Ararso Baru , Bekelcho Tariku , Woldemeskel Asfawosen , Tefera Kibreyesus , Eyob Degefe
Published: June 2022

Background

Unplanned pregnancy is an important public health problem in both the developing and developed world, as it may cause adverse social and health outcomes for mothers, children, and families as a whole. London Measure of Unplanned Pregnancy (LMUP) has been formally and informally validated in multiple and diverse settings. However, there is a dearth of literature on the validation of LMUP in Ethiopia either in the Amharic version or other languages.

Objective

The general objective of this study was to translate the LMUP into Amharic and evaluate its psychometric properties in a sample of Amharic-speaking women receiving antenatal care (ANC) service at public health facilities in Arbaminch and Birbir towns.

Methods

A cross-sectional study design was used for the study. Forward and backward translation of original English LMUP to Amharic was done. A cognitive interview using a pretested structured questionnaire was used to collect the data from respondents. The collected data was analyzed using SPSS version 25. Reliability was assessed using Cronbach’s alpha, inter-item correlations, and corrected item-total correlations while construct validity was assessed using principal components analysis and hypothesis testing.

Results

Data was collected from 320 women attending antennal care services at selected public health care facilities. LMUP range of 1to 11 was captured. The prevalence of unplanned pregnancies was 19(5.9%), while 136(42.5 were ambivalent and 165(51.6%) were planned pregnancies. The reliability testing demonstrated acceptable internal consistency (Cronbach’s alpha = 0.799) and the validity testing confirmed the unidimensional structure of the scale. In addition, all hypotheses were confirmed.

Conclusions

Amharic version of LMUP is a valid and reliable tool to measure pregnancy intention so that it can be used by Amharic speaking population in Ethiopia. It can also be used in research studies among Amharic-speaking women to measure unplanned pregnancy.
Journalism Research That Matters, Valérie Bélair-Gagnon and Nikki Usher (Eds) (2021)
Authors: Hirst Martin
Published: June 2022

Review of: Journalism Research That Matters, Valérie Bélair-Gagnon and Nikki Usher (Eds) (2021)

New York: Oxford University Press, 272 pp.,

ISBN 978-0-19753-847-0, h/bk, $177.87

ISBN 978-0-19753-848-7, p/bk, $48.01

ISBN 978-0-19753-847-0, e-book, $26.13
Disrupting Investigative Journalism: Moment of Death or Dramatic Rebirth?, Amanda Gearing (2021)
Authors: Harkin Janet M.
Published: June 2022

Review of: Disrupting Investigative Journalism: Moment of Death or Dramatic Rebirth?, Amanda Gearing (2021)

Oxford: Routledge Focus, 138 pp.,

ISBN 978-0-36769-001-4, h/bk, $75.99

ISBN 978-1-00313-998-0, e/bk, $26.39