bluuebunny/crossref_metadata_2025 huggingface dataset:
Roadmap on commercialization of metal halide perovskite photovoltaics
Authors: Feng Shien-Ping , Cheng Yuanhang , Yip Hin-Lap , Zhong Yufei , Fong Patrick W K , Li Gang , Ng Annie , Chen Cong , Castriotta Luigi Angelo , Matteocci Fabio , Vesce Luigi , Saranin Danila , Carlo Aldo Di , Wang Puqun , Wei Ho Jian , Hou Yi , Lin Fen , Aberle Armin G , Song Zhaoning , Yan Yanfa , Chen Xu , Yang Yang (Michael) , Syed Ali Asgher , Ahmad Ishaq , Leung Tiklun , Wang Yantao , Lin JingYang , Ng Alan Man Ching , Li Yin , Ebadi Firouzeh , Tress Wolfgang , Richardson Giles , Ge Chuangye , Hu Hanlin , Karimipour Masoud , Baumann Fanny , Tabah Kenedy , Pereyra Carlos , Raga Sonia R , Xie Haibing , Lira-Cantu Monica , Khenkin Mark V , Visoly-Fisher Iris , Katz Eugene A , Vaynzof Yana , Vidal Rosario , Yu Guicheng , Lin Haoran , Weng Shuchen , Wang Shifeng , Djurišić Aleksandra B
Published: March 2023

Perovskite solar cells (PSCs) represent one of the most promising emerging photovoltaic technologies due to their high power conversion efficiency. However, despite the huge progress made not only in terms of the efficiency achieved, but also fundamental understanding of the relevant physics of the devices and issues which affect their efficiency and stability, there are still unresolved problems and obstacles on the path toward commercialization of this promising technology. In this roadmap, we aim to provide a concise and up to date summary of outstanding issues and challenges, and the progress made toward addressing these issues. While the format of this article is not meant to be a comprehensive review of the topic, it provides a collection of the viewpoints of the experts in the field, which covers a broad range of topics related to PSC commercialization, including those relevant for manufacturing (scaling up, different types of devices), operation and stability (various factors), and environmental issues (in particular the use of lead). We hope that the article will provide a useful resource for researchers in the field and that it will facilitate discussions and move forward toward addressing the outstanding challenges in this fast-developing field.
Investigating spatial macroscopic metastability of perovskite solar cells with voltage dependent photoluminescence imaging
Authors: Koutsourakis George , Worsley Carys , Spence Michael , Blakesley James C , Watson Trystan M , Carnie Matt , Castro Fernando A
Published: March 2023

Metastability is a characteristic feature of perovskite solar cell (PSC) devices that affects power rating measurements and general electrical behaviour. In this work the metastability of different types of PSC devices is investigated through current–voltage (I–V) testing and voltage dependent photoluminescence (PL-V) imaging. We show that advanced I–V parameter acquisition methods need to be applied for accurate PSC performance evaluation, and that misleading results can be obtained when using simple fast I–V curves, which can lead to incorrect estimation of cell efficiency. The method, as applied in this work, can also distinguish between metastability and degradation, which is a crucial step towards reporting stabilised efficiencies of PSC devices. PL-V is then used to investigate temporal and spatial PL response at different voltage steps. In addition to the impact on current response, metastability effects are clearly observed in the spatial PL response of different types of PSCs. The results imply that a high density of local defects and non-uniformities leads to increased lateral metastability visible in PL-V measurements, which is directly linked to electrical metastability. This work indicates that existing quantitative PL imaging methods and point-based PL measurements of PSC devices may need to be revisited, as assumptions such as the absence of lateral currents or uniform voltage bias across a cell area may not be valid.
Natural ventilation versus air pollution: assessing the impact of outdoor pollution on natural ventilation potential in informal settlements in India
Authors: Nihar Kopal , Nutkiewicz Alex , Jain Rishee K
Published: March 2023

Despite the proven benefits of natural ventilation (NV) as an effective low-carbon solution to meet growing cooling demand, its effectiveness can be constrained by poor outdoor air quality. Here, we propose a modeling approach that integrates highly granular air pollution data with a coupled EnergyPlus and differential equation airflow model to evaluate how NV potential for space cooling changes when accounting for air pollution exposure (PM2.5). Given the high vulnerability of low-income populations to air pollution and the dearth of energy and thermal comfort research on informal settlements, we applied our model to a typical informal settlement residence in two large Indian cities: New Delhi and Bangalore. Our results indicate that outdoor PM2.5 levels have a significant impact on NV potential especially in highly polluted cities like New Delhi. However, we found that low-cost filtration (MERV 14) increased the NV potential by 25% and protected occupants from harmful exposure to PM2.5 with a minor energy penalty of 6%. We further find that adoption of low-cost filtration is a viable low-carbon solution pathway as it provides both thermal comfort and exposure protection at 65% less energy intensity—energy intensity reduced to 60 kWh m−2 from 173.5 kWh m−2 in case of adoption of potentially unaffordable full mechanical air conditioning. Our work highlights ample opportunities for reducing both air pollution and energy consumption in informal settlements across major Indian cities. Finally, our work can guide building designers and policymakers to reform building codes for adopting low-cost air filtration coupled with NV and subsequently reduce energy demand and associated environmental emissions.
Sparse trace tests
Authors: Brysiewicz Taylor , Burr Michael
Published: March 2023

We establish how the coefficients of a sparse polynomial system influence the sum (or the trace) of its zeros. As an application, we develop numerical tests for verifying whether a set of solutions to a sparse system is complete. These algorithms extend the classical trace test in numerical algebraic geometry. Our results rely on both the analysis of the structure of sparse resultants as well as an extension of Esterov’s results on monodromy groups of sparse systems.
Product of difference sets of the set of primes
Authors: Goswami Sayan
Published: March 2023

In a recent work, A. Fish [Proc. Amer. Math. Soc. 146 (2018), pp. 3449–3453] proved that if

E

1

E_{1}

and

E

2

E_{2}

are two subsets of

Z

\mathbb {Z}

of positive upper Banach density, then there exists

k
∈

Z

k\in \mathbb {Z}

such that

k
⋅

Z

⊂

(

E

1

−

E

1

)

⋅

(

E

2

−

E

2

)

.

k\cdot \mathbb {Z}\subset \left (E_{1}-E_{1}\right )\cdot \left (E_{2}-E_{2}\right ).

In this article we will show that a similar result is true for the set of primes

P

\mathbb {P}

(which has density

0
0

). We will prove that there exists

k
∈

N

k\in \mathbb {N}

such that

k
⋅

N

⊂

(

P

−

P

)

⋅

(

P

−

P

)

,

k\cdot \mathbb {N}\subset \left (\mathbb {P}-\mathbb {P}\right )\cdot \left (\mathbb {P}-\mathbb {P}\right ),

where

P

−

P

=

{
p
−
q
:
p
>
q
 and 
p
,
q
∈

P

}

.

\mathbb {P}-\mathbb {P}=\left \{ p-q:p>q\text { and }p,q\in \mathbb {P}\right \} .
Admissibility and nonuniform exponential dichotomies for difference equations without bounded growth or Lyapunov norms
Authors: Wu Mengda , Xia Yonghui
Published: March 2023

Many previous works used the admissibility of function classes to characterize nonuniform exponential dichotomy (for short, NEDs) by employing Lyapunov norms. Recently, L. Zhou and W. Zhang [J. Funct. Anal. 271 (2016), pp. 1087–1129] characterized NEDs without Lyapunov norms. They utilized two admissible pairs of function classes and an assumption on certain subspaces to describe NEDs under the prerequisite of bounded growth, which plays an essential role in their arguments. However, in this paper, we remove the condition of bounded growth when characterizing NEDs. Neither bounded growth nor Lyapunov norms are used to describe NEDs in this paper.
A note on the existence of stationary vortex patches for the SQG equation in bounded domain
Authors: Cao Daomin , Lai Shanfa , Qin Guolin
Published: March 2023

By studying the contour dynamics equation and using the implicit function theorem, we prove the existence of stationary vortex patches with fixed vorticity and total flux for each patch for the surface quasi-geostrophic equation in a bounded domain near non-degenerate critical points of the Kirchhoff-Routh function.
ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum
Authors: McCoy Ciaran J. , Paupelin-Vaucelle Humbeline , Gorilak Peter , Beneke Tom , Varga Vladimir , Gluenz Eva
Published: March 2023

Knockout phenotypes in Leishmania and detection of ULK4 ciliary localization in mice show that ULK4 and Fused/STK36 interact in a conserved pathway for stable assembly of motile cilia. This study describes severe structural defects in Leishmania flagella resulting from the loss of ULK4 or Fused/STK36 and shows evidence from BioID and co-immunoprecipitation for a direct interaction of Fused/STK36 with the pseudokinase ULK4.
The Arp2/3 complex enhances cell migration on elastic substrates
Authors: Mair Devin B. , Elmasli Ceylin , Kim June Hyung , Barreto Amanda D. , Ding Supeng , Gu Luo , Weinberg Seth H. , Kim Taeyoon , Kim Deok-Ho , Li Rong
Published: March 2023

The Arp 2/3 complex, a nucleator of branched actin, is shown to provide multiple distinct mechanical advantages to migrating glioblastoma cells. These include both decreased substrate stress and increased parallel focal adhesion interactions, preventing failure of cell–-substrate interactions.
Regulation of neurofilament length and transport by a dynamic cycle of phospho-dependent polymer severing and annealing
Authors: Uchida Atsuko , Peng Juan , Brown Anthony
Published: March 2023

It is demonstrated that neurofilament length and transport are regulated by a dynamic cycle of neurofilament polymer severing and end-to-end annealing. An enzymatic severing mechanism for neurofilaments involving N-terminal phosphorylation of their constituent polypeptides is proposed.
Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke
Authors: Patzwaldt Kristin , Berezhnoy Georgy , Ionescu Tudor , Schramm Linda , Wang Yi , Owczorz Miriam , Calderón Eduardo , Poli Sven , Serna Higuita Lina M , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Herfert Kristina , Pichler Bernd , Trautwein Christoph , Castaneda-Vega Salvador
Published: March 2023

Ambroxol is a well-known mucolytic expectorant, which has gained much attention in amyotrophic lateral sclerosis, Parkinson’s and Gaucher’s disease. A specific focus has been placed on ambroxol’s glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson’s disease. However, ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that ambroxol could have a direct impact on neuronal rescue if administered directly after ischaemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, oedema, white matter integrity, resting state functional MRI and behaviour for 1 month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex vivo nuclear magnetic resonance spectroscopy.

Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic oedema, reduced white matter degeneration, reduced necrosis, improved behavioural outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post-stroke proposes several metabolites that are capable of minimizing post-ischaemic damage and that presented prominent shifts during ambroxol treatment in comparison to controls. Taking everything together, we propose that ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of ambroxol administration following stroke onset reduced ischaemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.
Design, construction and performance evaluation of paddy rice solar drum dryer equipped with perforated drum
Authors: Leilayi Maedeh , Arabhosseini Akbar , Kianmehr Mohammad Hossein , Amiri Heman
Published: March 2023

A solar drum dryer was designed and constructed for paddy drying, including a fixed outer drum and inner perforated drum, which rotated at the desired rotational speed inside the outer drum. The maximum capacity of the dryer was 10 000 g. The rotational speed of the inner drum was controlled. The thermal energy required for the dryer was provided by a solar absorber plate. The dryer performance was examined at three levels of rotational speed (0.21, 0.42 and 0.84 r.p.m.), drum slope (1°, 1.5° and 2°) and air velocity (1.7, 1.8 and 1.9    m.s−1). The diameter of the drum was the geometrical parameter that affected the movement of the particles and the ratio of the particle diameter to the drum diameter changed with the change in the drum diameter. Therefore, increasing the diameter of the drum caused a reduction in the repose angle of the paddy without any effect on the filling angle. The displacement of the product along the drum increased with increasing slope and rotational speed. At the lowest air velocity, the time required to remove moisture (<13%) was less. The results showed a significant reduction in cracked brown rice for the paddy dried by the drum dryer at 43–46°C compared with those dried using a batch dryer. The highest stress-cracking index (11) was observed for the paddy with an initial moisture of 16%. The results showed that for proportional final moisture content, a longer drum should be considered to intensify the slope and rotational speed of the inner drum.
Decomposition analysis of CO2 emissions of electricity and carbon-reduction policy implication: a study of a province in China based on the logarithmic mean Divisia index method
Authors: Yang Fuyuan , Yang Xiaobin , Tian Xueqin , Wang Xinlei , Xu Tong
Published: March 2023

As the proportion of electricity in final energy consumption gradually increases, CO2 emissions reduction actions in the power system will become the key to achieving China’s carbon-peak and carbon-neutrality goals. It is essential to analyse and quantify the driving forces of CO2 emissions from electricity generation in the fossil-rich area in China. This paper aims to identify the characteristics of CO2 emissions generated by electricity and provide a basis for formulating CO2-reduction policies in power systems. First, we analyse the current state of CO2 emissions from electricity generation in Anhui Province that was dominated by fossil energy during the period 2010–19. Then, we apply the logarithmic mean Divisia index method to find the nature of the factors influencing the changes in CO2 emissions. Finally, we analyse the CO2-reduction measures of each side of the source–network–load–storage of the power system in Anhui through a power-system carbon-reduction path analysis model proposed in this study and provide policy suggestions. The results showed the following. (i) CO2 emissions in Anhui Province continued to increase from 2010 to 2019 and the trend in the growth rate of CO2 emissions presented approximately a u-shaped curve. (ii) Economic activity has always been the dominant factor driving the growth of electricity CO2 emissions. The increase in the proportion of renewable energy in power generation, the improvement in thermal power-conversion efficiency and the decrease in the intensity of power consumption are the three major driving factors for the reduction in CO2 emissions from power generation in Anhui. (iii) The CO2-reduction measures of the power system are provided in each link of the source–network–load–storage, such as developing the photovoltaic industry and building energy storage, upgrading and transforming coal-fired power stations, reducing the loss rate of transmission lines on the grid side and improving the efficiency of the utilization of electricity on the user side.
Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients
Authors: Mikulska Malgorzata , Sepulcri Chiara , Dentone Chiara , Magne Federica , Balletto Elisa , Baldi Federico , Labate Laura , Russo Chiara , Mirabella Michele , Magnasco Laura , Di Grazia Carmen , Ghiggi Chiara , Raiola Anna Maria , Giacobbe Daniele Roberto , Vena Antonio , Beltramini Sabrina , Bruzzone Bianca , Lemoli Roberto M , Angelucci Emanuele , Bassetti Matteo
Published: March 2023

Background

Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients.

Methods

We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up.

Results

Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction).

Conclusions

Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.
Predicting evolution in experimental range expansions of an aquatic model system
Authors: Zilio Giacomo , Krenek Sascha , Gougat-Barbera Claire , Fronhofer Emanuel A , Kaltz Oliver
Published: March 2023

Predicting range expansion dynamics is an important goal of both fundamental and applied research in conservation and global change biology. However, this is challenging if ecological and evolutionary processes occur on the same time scale. Using the freshwater ciliate Paramecium caudatum, we combined experimental evolution and mathematical modeling to assess the predictability of evolutionary change during range expansions. In the experiment, we followed ecological dynamics and trait evolution in independently replicated microcosm populations in range core and front treatments, where episodes of natural dispersal alternated with periods of population growth. These eco-evolutionary conditions were recreated in a predictive mathematical model, parametrized with dispersal and growth data of the 20 founder strains in the experiment. We found that short-term evolution was driven by selection for increased dispersal in the front treatment and general selection for higher growth rates in all treatments. There was a good quantitative match between predicted and observed trait changes. Phenotypic divergence was further mirrored by genetic divergence between range core and front treatments. In each treatment, we found the repeated fixation of the same cytochrome c oxidase I (COI) marker genotype, carried by strains that also were the most likely winners in our model. Long-term evolution in the experimental range front lines resulted in the emergence of a dispersal syndrome, namely a competition—colonization trade-off. Altogether, both model and experiment highlight the potential importance of dispersal evolution as a driver of range expansions. Thus, evolution at range fronts may follow predictable trajectories, at least for simple scenarios, and predicting these dynamics may be possible from knowledge of few key parameters.
Characteristics of The Bleached Microbiome of The Generalist CoralPocillopora damicornisfrom Two Distinct Reef Habitats
Authors: Bergman J L , Ricci F , Leggat W , Ainsworth T D
Published: March 2023

Synopsis

Generalist coral species may play an important role in predicting, managing, and responding to the growing coral reef crisis as sea surface temperatures are rising and reef wide bleaching events are becoming more common. Pocilloporids are amongst the most widely distributed and studied of generalist corals, characterized by a broad geographic distribution, phenotypic plasticity, and tolerance of sub-optimal conditions for coral recruitment and survival. Emerging research indicates that microbial communities associated with Pocilloporid corals may be contributing to their persistence on coral reefs impacted by thermal stress; however, we lack detailed information on shifts in the coral–bacterial symbiosis during bleaching events across many of the reef habitats these corals are found. Here, we characterized the bacterial communities of healthy and bleached Pocillopora damicornis corals during the bleaching events that occurred during the austral summer of 2020 on Heron Island, on the southern Great Barrier Reef, and the austral summer of 2019 on Lord Howe Island, the most southerly coral reef in Australia. Regardless of reef location, significant differences in α and β diversities, core bacterial community, and inferred functional profile of the bleached microbiome of P. damicornis were not detected. Consistent with previous reports, patterns in the Pocilloporid coral microbiome, including no increase in pathogenic taxa or evidence of dysbiosis, are conserved during bleaching responses. We hypothesize that the resilience of holobiont interactions may aid the Pocilloporids to survive Symbiodiniaceae loss and contribute to the success of Pocilloporids.
Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?
Authors: Vasikasin Vasin , Rawson Timothy M , Holmes Alison H , Otter Jonathan
Published: March 2023

The emergence of carbapenem-resistant organisms (CROs) is a significant global threat. Reduction of carbapenem consumption can decrease CROs. In the global endemic era of ESBL-producing bacteria, carbapenems are considered the treatment of choice, leading to challenge in limiting carbapenem use. This review describes the role of precision prescribing for prevention of CROs. This involves improving antibiotic selection, dosing and shortening duration. The effect of different antibiotics, dosing and duration on CRO development are explored. Available options for precision prescribing, gaps in the scientific evidence, and areas for future research are also presented.
Central Banks and Climate Change: Mission Impossible?
Authors: Cullen Jay
Published: March 2023

There is growing presumption that central banks have a significant role to play in addressing environmental challenges, especially climate change. This article explains, on the basis of both theoretical and empirical evidence, that attempting to use existing central bank tools and powers to tackle climate change will prove inadequate to tackle the issue(s) at hand. From a positivist perspective at least—and contrary to the claims made in the literature—the tools that central banks possess are insufficient to make any meaningful contribution to emissions reductions and prevent global heating. This is because many of the proposals made by academics, regulators, and legislators to expand the central bank toolkit to equip banks to tackle climate change suffer from deep conceptual and practical drawbacks when applied in this domain. These critical weaknesses mean that the policy prescriptions that flow from them will be of limited impact; this would likely be the case even if central banks were to obviate their mandates more explicitly and attempt to use such tools to address climate change directly. In so doing, they waste valuable political and economic capital that might be usefully deployed in tackling climate change. The obstacles to using these tools are not political or legal; they are inherent in their operation.
Robotic-assisted distal pancreatectomy with splenectomy in a paediatric patient for solid pseudopapillary tumour
Authors: Sergi William , Depalma Norma , Marchese Tiziana , Manoochehri Farshad , D’Ugo Stefano , Garritano Stefano , Botrugno Ivan , Chiappini Ambra , Libia Annarita , Atzeni Carlo Olla , Stasi Elisa , Spampinato Marcello G
Published: March 2023

Solid pseudopapillary tumour is a rare low-grade malignant potential carcinoma of the pancreas that typically occurs in females in their third decade. It most commonly occurs in the tail of the pancreas, although any site can be affected. Surgical resection is the standard treatment and offers an excellent prognosis. We report a case of a 17-year-old female with an acute onset abdominal pain and a radiological diagnosis of a cystic lesion in the distal pancreas. A robotic-assisted distal pancreatectomy with splenectomy was performed. Robotic-assisted surgery is an emerging technique for the treatment of pancreatic neoplasms. This approach can be considered for younger patients, thanks to the potential advantages of the robotic Da Vinci Xi System.
Acinar cystic transformation of the pancreas causing progressive main pancreatic duct dilation: a diagnostic dilemma
Authors: Sebastian Elizabeth , Longano Anthony , Wei Matthew Y K , Goonawardena Janindu , Bull Nicholas , Hassen Sayed
Published: March 2023

Acinar cystic transformation (ACT) of the pancreas is a rare benign lesion. We describe a case of ACT with progressive main pancreatic duct dilation concerning for malignancy, not previously described. We discuss the difficulties associated with imaging and biopsy in differentiating this pathology from other cystic lesions, including intraductal mucinous papillary neoplasms.
The case of the missing spacer!
Authors: Boerkamp Andrea , De Robles Marie Shella
Published: March 2023

The SpaceOAR Vue hydrogel system was developed to reduce the toxicity to the rectum following radiation therapy for prostate cancer. Initial trial data reported the product as overall effective and safe. However, a few additional observed complications have likely been brought on by its increased utilization. The case presented herein describes rectal erosion, with abscess and rectal fistula formation, associated with the use of the SpaceOAR Vue hydrogel system. The SpaceOAR Vue hydrogel system was subsequently found to be absent between radiotherapy treatments and was thought to have been passed rectally through the fistula. The benefits and complications of the SpaceOAR Vue hydrogel system are discussed, as well as key factors to consider as the recommendation of routine use increases.
GMC collisions as triggers of star formation – VIII. The core mass function
Authors: Hsu Chia-Jung , Tan Jonathan C , Christie Duncan , Cheng Yu , O’Neill Theo J
Published: March 2023

Compression in giant molecular cloud (GMC) collisions is a promising mechanism to trigger the formation of massive star clusters and OB associations. We simulate colliding and non-colliding magnetized GMCs and examine the properties of pre-stellar cores, selected from projected mass surface density maps, including after synthetic ALMA observations. We then examine core properties, including mass, size, density, velocity, velocity dispersion, temperature, and magnetic field strength. After 4 Myr, ∼1000 cores have formed in the GMC collision, and the high-mass end of the core mass function (CMF) can be fit by a power-law dN/dlogM ∝ M−α with α ≃ 0.7, i.e. relatively top heavy compared to a Salpeter mass function. Depending on how cores are identified, a break in the power law can appear around a few $\times 10\, \mathrm{M}_\odot$. The non-colliding GMCs form fewer cores with a CMF with α ≃ 0.8–1.2, i.e. closer to the Salpeter index. We compare the properties of these CMFs to those of several observed samples of cores. Considering other properties, cores formed from colliding clouds are typically warmer, have more disturbed internal kinematics, and are more likely to be gravitational unbound, than cores formed from non-colliding GMCs. The dynamical state of the protocluster of cores formed in the GMC–GMC collision is intrinsically subvirial but can appear to be supervirial if the total mass measurement is affected by observations that miss mass on large scales or at low densities.
Diverse targets ofSMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy
Authors: Ottesen Eric W , Singh Natalia N , Luo Diou , Kaas Bailey , Gillette Benjamin J , Seo Joonbae , Jorgensen Hannah J , Singh Ravindra N
Published: March 2023

Designing an RNA-interacting molecule that displays high therapeutic efficacy while retaining specificity within a broad concentration range remains a challenging task. Risdiplam is an FDA-approved small molecule for the treatment of spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Branaplam is another small molecule which has undergone clinical trials. The therapeutic merit of both compounds is based on their ability to restore body-wide inclusion of Survival Motor Neuron 2 (SMN2) exon 7 upon oral administration. Here we compare the transcriptome-wide off-target effects of these compounds in SMA patient cells. We captured concentration-dependent compound-specific changes, including aberrant expression of genes associated with DNA replication, cell cycle, RNA metabolism, cell signaling and metabolic pathways. Both compounds triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage. Our results of minigenes expressed in HeLa cells provide mechanistic insights into how these molecules targeted towards a single gene produce different off-target effects. We show the advantages of combined treatments with low doses of risdiplam and branaplam. Our findings are instructive for devising better dosing regimens as well as for developing the next generation of small molecule therapeutics aimed at splicing modulation.
A complementary approach for genetic diagnosis of inborn errors of immunity using proteogenomic analysis
Authors: Sakura Fumiaki , Noma Kosuke , Asano Takaki , Tanita Kay , Toyofuku Etsushi , Kato Kentaro , Tsumura Miyuki , Nihira Hiroshi , Izawa Kazushi , Mitsui-Sekinaka Kanako , Konno Ryo , Kawashima Yusuke , Mizoguchi Yoko , Karakawa Shuhei , Hayakawa Seiichi , Kawaguchi Hiroshi , Imai Kohsuke , Nonoyama Shigeaki , Yasumi Takahiro , Ohnishi Hidenori , Kanegane Hirokazu , Ohara Osamu , Okada Satoshi
Published: March 2023

Advances in next-generation sequencing technology have identified many genes responsible for inborn errors of immunity (IEI). However, there is still room for improvement in the efficiency of genetic diagnosis. Recently, RNA sequencing and proteomics using peripheral blood mononuclear cells (PBMCs) have gained attention, but only some studies have integrated these analyses in IEI. Moreover, previous proteomic studies for PBMCs have achieved limited coverage (approximately 3000 proteins). More comprehensive data are needed to gain valuable insights into the molecular mechanisms underlying IEI. Here, we propose a state-of-the-art method for diagnosing IEI using PBMCs proteomics integrated with targeted RNA sequencing (T-RNA-seq), providing unique insights into the pathogenesis of IEI. This study analyzed 70 IEI patients whose genetic etiology had not been identified by genetic analysis. In-depth proteomics identified 6498 proteins, which covered 63% of 527 genes identified in T-RNA-seq, allowing us to examine the molecular cause of IEI and immune cell defects. This integrated analysis identified the disease-causing genes in four cases undiagnosed in previous genetic studies. Three of them could be diagnosed by T-RNA-seq, while the other could only be diagnosed by proteomics. Moreover, this integrated analysis showed high protein–mRNA correlations in B- and T-cell-specific genes, and their expression profiles identified patients with immune cell dysfunction. These results indicate that integrated analysis improves the efficiency of genetic diagnosis and provides a deep understanding of the immune cell dysfunction underlying the etiology of IEI. Our novel approach demonstrates the complementary role of proteogenomic analysis in the genetic diagnosis and characterization of IEI.
The impact of social determinants of health on the presentation, management and outcomes of systemic lupus erythematosus
Authors: Williams Jessica N , Drenkard Cristina , Lim S Sam
Published: March 2023

Disparities in SLE rates and outcomes have been attributed to genetic and hormonal factors, cigarette smoking and environmental pollutants. However, a growing body of research indicates that social determinants of health (SDH) also have substantial impact on the disparities that characterize SLE. According to the World Health Organization, SDH are defined as ‘the conditions in which people are born, grow, work, live, and age’, account for 30–55% of health outcomes, and adversely impact health outcomes among those of low socioeconomic status and stigmatized racial/ethnic groups. We reviewed the impact of key SDH on SLE presentation, management and outcomes, including income, education, neighbourhood factors, healthcare access, discrimination and social support. We found that adverse SDH conditions may lead to more severe SLE with increased morbidity and mortality, and that SDH affect SLE management by dictating the most feasible monitoring and treatment plan for each individual patient based on his or her specific life circumstances (for example, based on health insurance status, distance to nearest provider and/or drug affordability). SDH also have a significant impact on SLE outcomes, with worse disease and psychosocial outcomes associated with lower income level, lower educational attainment, disadvantaged neighbourhoods, lack of health insurance or public health insurance in the USA, travel burden to nearest provider, anti-Black racism and lower social support. Future efforts to improve the management and outcomes of patients with SLE must combat the societal, economic and political forces that perpetuate these inequities.
A Scoping Review of Retrieval Practice (Test-Enhanced Learning) in Nursing Education
Authors: Van Hoof Thomas J. , Leary Catherine M. , Banfi Valori , Polifroni E. Carol
Published: March 2023

AIM

The aim of this study was to determine the status of retrieval practice in original research of nursing education.

BACKGROUND

The science of learning is an emerging interdisciplinary field that offers evidence-based strategies to improve learning. One of the most highly effective strategies is retrieval practice, which involves recalling previously learned information from long-term memory prior to additional study.

METHOD

Searching PubMed, CINAHL, Scopus, Psych INFO, and ERIC, an interprofessional team followed a formal scoping review framework and utilized the PRISMA Extension for Scoping Reviews to report the findings.

RESULTS

The review included 25 research studies, with all but one at the prelicensure level. Quantitative designs were most common, and outcomes reflected objective and subjective measures. If present, terms were varied and inconsistent with supporting research. Documentation of many characteristics was lacking.

CONCLUSION

Retrieval practice is an increasingly common strategy being studied at the prelicensure level. Opportunities for improvement include consistent use of standard terminology, documentation of important characteristics, and more attention to subjective outcomes and to graduate and continuing education levels.
Who Benefits From Allowing the Physis to Grow in Slipped Capital Femoral Epiphysis?
Authors: Winger Breanna J. , Dobbe Ashlee M. , Cheng Tegan L. , Little David G. , Gibbons Paul J.
Published: March 2023

Background:

The globally acknowledged treatment for mild to moderate slipped capital femoral epiphysis (SCFE) is single screw in situ fixation, also used for prophylactic contralateral fixation. The Free-Gliding Screw (FG; Pega Medical) is a 2-part free-extending screw system designed to allow the growth of the proximal femur. We aimed to analyze the relationship between skeletal maturity and potential growth of the proximal physis and remodeling of the femoral neck using this implant.

Materials and Methods:

Females below 12 years and males below 14 years undergoing in situ fixation for stable SCFE or prophylactic fixation were treated using the implant. Three elements of the modified Oxford Bone (mOB3) score were used to measure maturity (triradiate cartilage, head of the femur, and greater trochanter). Radiographs were analyzed immediately postoperatively and at a minimum of 2 years for a change in screw length, posterior-sloping angle, articulotrochanteric distance, α angle, and head-neck offset.

Results:

The study group comprised 30 (F:M=12:18) of 39 hips treated with SCFE and 22 (F:M=13:9) of 29 hips managed prophylactically using the free-Gliding screw. In the therapeutic group, chronologic age was a less valuable predictor of future screw lengthening than mOB3. An mOB3of ≤13 predicted future growth of >6 mm but did not reach statistical significance (P=0.07). Patients with open triradiates showed a mean screw lengthening of 6.6 mm compared with those with closed triradiates (4.0 mm), but this did not reach significance (P=0.12). In those with mOB3≤13, the α angle reduced significantly (P<0.01) and the head-neck offset increased significantly, suggesting remodeling. There was no change in these parameters when mOB3≥14. In the prophylactic group, change in screw length was significant with mOB3of ≤13 (mean=8.0 mm,P<0.05), as was the presence of an open triradiate cartilage (mean=7.7 mm,P<0.05). In both cohorts, posterior-sloping angle and articulotrochanteric distance did not change, indicating no slip progression in either treatment or prophylactic groups and minimal effect on the proximal physeal growth relative to the greater trochanter.

Conclusions:

Growing screw constructs can halt slip progression while allowing proximal femoral growth in young patients with SCFE. Ongoing growth is better when the implant is used for prophylactic fixation. The results in treated SCFE need to be expanded to demonstrate a clinically meaningful cut-off for significant growth, but SCFE patients with an open triradiate remodel significantly more than those where it is closed.

Level of Evidence:

Level III—retrospective comparative study.
Understanding the Impact of Bowel Dysfunction on Quality of Life after Rectal Cancer Surgery from the Patient’s Perspective
Authors: Maalouf Michael F. , Robitaille Stephan , Penta Ruxandra , Pook Makena , Liberman A. Sender , Fiore Julio F. , Feldman Liane S. , Lee Lawrence
Published: March 2023

BACKGROUND:

Bowel dysfunction is an important consequence of rectal cancer surgery and the specific quality of life domains that are affected remain unclear and unaddressed by generic surveys.

OBJECTIVE:

To identify quality of life domains most affected by rectal cancer surgery.

DESIGN:

Qualitative content analysis.

SETTINGS:

Semi-structured interviews conducted by telephone with patients recruited from a single university-affiliated colorectal referral center.

PATIENTS:

Adult patients who underwent rectal cancer surgery with sphincter preservation from 07/2017 to 07/2020. Patients were excluded if their surgery was <1 year since the recruitment date, received a permanent stoma, or developed recurrence or metastasis.

MAIN OUTCOME MEASURES:

Bowel dysfunction was evaluated via the low anterior resection syndrome score. Interview transcripts were coded by 2 independent reviewers and evaluated for concordance. Qualitative content analysis was used to identify themes, with their frequency of occurrence quantified (percent total number of interviews).

RESULTS:

A total of 54 patient interviews were conducted. Analysis revealed 5 quality of life related themes impacted by bowel dysfunction: experiencing psychological and emotional stress, challenging roles and relationships within society, encountering physical limitations, restricting leisure and recreational activities, and self-empowerment and adapting to change. Patients with minor and major bowel dysfunction were more likely to report disruption to social activities and role as a sexual partner versus those with no bowel dysfunction. Patients with major bowel dysfunction were more likely to report effects on sleep versus those with no and minor bowel dysfunction.

LIMITATIONS:

Single center, self-reported, and observer bias.

CONCLUSION:

The impact of bowel dysfunction on quality of life includes a wide range of themes that extend beyond the traditional measures. These results may help better inform patients in the preoperative setting and serve as a basis for the development of a more patient-centered quality of life survey.
Does Rectoanal Intussusception Limit Improvements in Clinical Outcome and Quality of Life after Sacral Nerve Stimulation for Fecal Incontinence?
Authors: Dawes Aaron J. , Mariscal Juan , White Peter , Midura Emily F. , Sirany Anne E. , Lowry Ann C. , Jensen Christine C. , Thorsen Amy J.
Published: March 2023

BACKGROUND:

Sacral nerve stimulation is a treatment option for severe, medically refractory fecal incontinence, although its use in patients with anatomic abnormalities remains controversial.

OBJECTIVE:

To determine if patients with rectoanal intussusception achieve similar benefits from device implantation to patients without rectoanal intussusception

DESIGN:

Retrospective review of a prospectively maintained database. Demographics and clinical data were collected for each patient, including pre-operative pelvic floor testing. Defecographies were re-analyzed in a blinded fashion. Pre-operative rectoanal intussusception was determined based on the Oxford system (grade III-IV vs. not; grade V excluded).

SETTINGS:

Academic-affiliated pelvic health center

PATIENTS:

All patients undergoing sacral nerve stimulation for fecal incontinence between July 2011 and July 2019

MAIN OUTCOME MEASURES:

Cleveland Clinic Florida Incontinence/Wexner Scores, Fecal Incontinence Severity Indices, Fecal Incontinence Quality of Life Indices at 1 year

RESULTS:

169 patients underwent sacral nerve stimulation for fecal incontinence during the study period. The average age was 60.3 years old and 91% were female. Forty-six patients (27.2%) had concomitant rectoanal intussusception (38 [22.5%] grade III and 8 [4.7%] grade IV). Before surgery, patients reported an average of 10.8 accidents per week and a Wexner score of 15.7 with no difference between patients with and without rectoanal intussusception (p = 0.22 and 0.95). At 1 year after surgery, the average Wexner score was 9.5. There was no difference in post-operative Wexner scores (10.4 vs. 9.2, p = 0.23) or improvement over time between patients with and without rectoanal intussusception (-6.7 vs. -5.7, p = 0.40). Similarly, there was no difference in quality of life or frequency of incontinence to liquid or solid stool.

LIMITATIONS:

Single institution, moderate sample size, incomplete survey response

CONCLUSION:

Concomitant rectoanal intussusception does not appear to affect clinical outcomes or quality of life after sacral nerve stimulation for fecal incontinence. Appropriate patients with fecal incontinence and rectoanal intussusception can be considered for sacral nerve stimulation placement.
The comparison of caesarean section bleeding between volatile and total intravenous anaesthesia in a Japanese nationwide database
Authors: Shimada Kensuke , Iwagami Masao , Makito Kanako , Shigemi Daisuke , Uda Kazuaki , Ishimaru Miho , Komiyama Jun , Morita Kojiro , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo , Tanaka Makoto , Tamiya Nanako
Published: March 2023

BACKGROUND

Volatile anaesthesia may increase blood loss because of the uterine-relaxing effect of the volatile anaesthetics during caesarean section under general anaesthesia.

OBJECTIVE

This study compared the bleeding risk during caesarean section between volatile anaesthesia and total intravenous anaesthesia (TIVA) using a nationwide inpatient database in Japan.

DESIGN

Observational study.

SETTING

Nationwide inpatient database in Japan from April 2012 to March 2020.

PATIENTS

Women who underwent caesarean section under general anaesthesia.

MAIN OUTCOME MEASURES

Volume of blood loss.

RESULTS

We identified 26 585 women, including 19 320 in the volatile anaesthesia group (mean age = 32.9 ± 5.5 years) and 7265 in the TIVA group (mean age = 32.8 ± 5.5 years). The mean blood loss was 1113 ± 909 and 1136 ± 944 ml and the proportion of blood transfusion was 14.7 and 16.0% in the volatile and TIVA groups, respectively. With conventional regression analyses, volatile anaesthesia was associated with a slightly lower risk of bleeding: the adjusted mean difference for blood loss (95% CI) was −56.1 (−81.4 to −30.7). However, in the instrumental variable analysis, volatile anaesthesia was associated with a higher risk of bleeding: adjusted mean difference for blood loss (95% CI) was 154.3 (112.4 to 196.3) ml.

CONCLUSION

This large observational study with instrumental variable analyses suggested an increased bleeding risk associated with volatile anaesthesia, and the results were not identical to those in the conventional regression analyses.