bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Perceptions of Decision-making and Quality-of-life Following Surgical Resection of Pancreatic Adenocarcinoma
Authors: Bleicher Josh , Place Aubrey , Harris Alex H. S. , Scaife Courtney L. , Huang Lyen C.
Published: March 2023

Background:

Pancreatic adenocarcinoma (PDAC) remains a highly lethal disease, with surgery, the only opportunity for cure, accompanied by high rates of morbidity. Understanding patients’ lived experiences after surgical resection of PDAC is critical to knowing whether the decision to undergo surgery was worth it for these patients.

Methods:

We performed a convergent, mixed-methods study with patients who underwent resection of PDAC between January 1, 2019, and January 8, 2020. Quantitative data (medical record review and 3 questionnaires) were analyzed using descriptive statistics. Qualitative data (semistructured interviews) were analyzed using the constant comparative method. Data were then compared for congruence.

Results:

Eighteen of 22 eligible participants completed interviews and 11 completed questionnaires. Data collection occurred at a median of 14.2 months (IQR 11.6–16.3) from surgery. We identified 4 main themes. First, persistent negative symptoms were common for patients, but patients adapt to these and are satisfied with their “new normal.” Second, patients have varied and continually evolving mindsets throughout their cancer journey. Third, despite decreased quality-of-life, patients have a high degree of satisfaction with their decision to pursue surgery. Finally, patients were okay with a passive role in decision-making around surgery. Despite variable involvement in decision-making and outcomes, no participants reported regret over the decision to pursue surgery.

Discussion:

This nuanced account of patients’ lived experiences following surgery for PDAC allows for an improved understanding of the impact of pancreatic resection on patients. Surgeons can use these data to improve preoperative counseling for patients with PDAC and help guide them to making the correct decisions about surgery.
Long-Term Outcomes of Venous Resections in Pancreatic Ductal Adenocarcinoma Patients
Authors: Sillesen Martin , Hansen Carsten Palnæs , Dencker Emilie Even , Burgdorf Stefan Kobbelgaard , Krohn Paul Suno , Stender Mogens Tornby , Fristrup Claus Wilki , Storkholm Jan Henrik
Published: March 2023

Objective:

To investigate whether pancreatic resections (PR) for pancreatic ductal adenocarcinoma (PDAC) is associated with worse survival when resection of the superior mesenteric vein/portal vein (SMV/PV) is required.

Background:

PR for PDAC with resection of the superior mesenteric vein/portal vein (SMV/PV, PR+V resection) may be associated with inferior overall survival (OS) compared with PR without the need for SMV/PV resection (PR–V). We hypothesized that PR+V results in lower OS compared with PR–V.

Method:

Retrospective study using data from the nationwide Danish Pancreatic Cancer Database from 2011 to 2020. Data on patients who underwent PR for PDAC were extracted. A group of PR patients found nonresectable on exploratory laparotomy (EXP) was also included. OS was assessed using Kaplan-Meier and Cox proportional hazards models adjusting for confounders (age, sex, R-resection level, chemotherapy, comorbidities, histology T and N classification, procedure subtype as well as tumor distance to the SMV/PV).

Results:

Overall, 2403 patients were identified. Six hundred two underwent exploration only (EXP group), whereas 412 underwent pancreatic resection with (PR+V group) and 1389 (PR–V) without SMV/PV resection. Five-year OS for the PR+V group was lower (20% vs 30%) compared with PR–V, although multivariate Cox proportional hazards modeling could not associate PR+V status with OS (Hazard ratio 1.11, P = 0.408).

Conclusion:

When correcting for confounders, PR+V was not associated with lower OS compared with PR–V.
Robotic Magnetic Surgery: Results From the First Prospective Clinical Trial
Authors: Romero-Velez Gustavo , Robles Ignacio , Jiménez Julio , Cabrera Carolina , Luengas Rafael , Portenier Dana , Kroh Matthew
Published: March 2023

Objectives:

To evaluate a novel Magnetic Robotic Platform during reduced-port laparoscopic surgery in a prospective, multicenter clinical trial.

Background:

Magnetic surgery has been developed to increase the benefits of minimally invasive surgery, with prior studies demonstrating its clinical benefits. Robotic-assisted surgery increases the surgeon’s control over the instruments, offering less dependency on an assistant. The synergism of both techniques may escalate these individual benefits.

Methods:

A prospective, multicenter, single-arm, open-label study was performed to assess the safety and performance of a robotic magnetic surgical system (Levita Robotic Platform). The investigational device was used during reduced-port laparoscopic cholecystectomy and laparoscopic bariatric surgery. The primary endpoints evaluated were safety and feasibility. Patients were followed for 30 days post-procedure.

Results:

Between May 2021 and December 2021, 30 patients undergoing laparoscopic surgery were recruited. There were 22 females and 8 males with a mean age of 39 years (22–69 years) and median body mass index of 33 kg/m2 (21.6–50.4 kg/m2). Procedures included 15 gastric sleeves, 14 cholecystectomies, and 1 Roux en-Y gastric bypass. The procedures were successfully performed by utilizing the robotic magnetic surgical system and a reduced-port technique in all 30 patients. No device-related serious adverse events were reported. The device provided adequate visualization and retraction in all cases.

Conclusions:

This clinical trial shows for the first time that this novel Magnetic Robotic Platform is safe and feasible in reduced-port laparoscopic cholecystectomy and laparoscopic bariatric surgery. This robotic platform brings the benefits of magnetic surgery in terms of reduction of incisions plus increasing the control for the surgeon.
Association of Hospital Bed Turnover With Patient Outcomes in Digestive Surgery
Authors: Pasquer Arnaud , Pascal Léa , Polazzi Stephanie , Skinner Sarah , Poncet Gilles , Lifante Jean-Christophe , Duclos Antoine
Published: March 2023

Objective:

To determine the influence of hospital bed turnover rate (BTR) on the occurrence of complications following minor or major digestive surgery.

Background:

Performance improvement in surgery aims at increasing productivity while preventing complications. It is unknown whether this relationship can be influenced by the complexity of surgery.

Methods:

A nationwide retrospective cohort study was conducted, based on generalized estimating equation modeling to determine the effect of hospital BTR on surgical outcomes, adjusting for patient mix and clustering within 631 public and private French hospitals. All patients who underwent minor or major digestive surgery between January 1, 2013 and December 31, 2018 were included. Hospital BTR was defined as the annual number of stays per bed for digestive surgery and categorized into tertiles. The primary endpoint was a composite measurement of events occurring within 30 days after surgery: inpatient death, extended intensive care unit (ICU) admission, and reoperation.

Results:

Rate of adverse events was 2.51% in low BTR hospitals versus 2.25% in high BTR hospitals for minor surgery, and 16.79% versus 16.83% for major surgery. Patients who underwent minor surgery in high BTR hospitals experienced lower complications (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.81–0.97; P = 0.009), mortality (OR, 0.87; 95% CI, 0.78–0.98, P = 0.02), ICU admission (OR, 0.83; 95% CI, 0.70–0.99; P = 0.03), and reoperation (OR, 0.91; 95% CI, 0.85–0.97; P = 0.002) compared to those in low BTR hospitals. Such differences were not consistently observed among patients admitted for major surgery.

Conclusions:

High turnover of patients in beds is beneficial for minor procedures, but questionable for major surgeries.
Long-term Outcomes and Factors Predicting Outcome of Ileal Pouch-Anal Anastomosis When Used Intentionally for Well-Defined Crohn’s Disease
Authors: Aviran Eyal , Assaf Dan , Zaghiyan Karen , Fleshner Phillip
Published: March 2023

BACKGROUND:

Crohn’s disease (CD) is considered a contraindication for ileal pouch-anal anastomosis (IPAA). Our prior study of IPAA when used intentionally for well-defined CD showed a high incidence of recurrent disease with a low incidence of pouch failure

OBJECTIVE:

Replicate these findings in a larger cohort over a longer period

DESIGN:

Retrospective review of a prospective inflammatory bowel disease registry

SETTINGS:

Large IBD referral center

PATIENTS:

Preoperative colorectal CD requiring surgery

INTERVENTION:

Ileal pouch-anal anastomosis

MAIN OUTCOME:

Long-term CD recurrence, pouch failure and pouch function

RESULTS:

Forty-six patients were identified. CD was diagnosed based on perianal disease (n = 18; 39%), small bowel disease (n = 16; 35%), noncaseating granuloma (n = 10; 22%) and discontinuous inflammation (colorectal skip lesions) (n = 11; 24%). After a median follow up of 93 (7-291) months, 22 (48%) patients developed recurrent CD based on afferent limb disease (n = 14; 30%) or pouch fistulizing disease (n = 8; 18%). Only 4 (9%) patients developed pouch failure. No clinical factor was associated with CD recurrence. Young age at the time of surgery and short duration of disease prior to IPAA were associated with pouch fistula recurrence (p = 0.003 and p = 0.03, respectively). Higher preoperative platelet count was the only clinical characteristic significantly associated with pouch failure (p = 0.02). Most patients (86%) reported excellent continence, with no urgency (67%) and median stool frequency of 6 (range, 3-9) per day.

LIMITATION:

Retrospective nature and relatively small sample size.

CONCLUSION:

This largest reported series examining the intentional use of IPAA in CD showed a high (48%) incidence of postoperative CD with a low (9%) incidence of pouch failure. Young age and short disease course prior to surgery were risk factors for poor outcome. Highly motivated patients with colorectal CD may consider an IPAA and avoid a definitive ileostomy.
Assessing Rates of Positive Surgical Margins After Standard Excision of Vulvar Melanomas
Authors: Cheraghlou Shayan , Doudican Nicole A. , Criscito Maressa C , Stevenson Mary L. , Carucci John A.
Published: March 2023

BACKGROUND

Vulvar melanoma is a rare malignancy with frequent recurrence and poor prognosis. National guidelines recommend wide local excision of these tumors with allowances for narrower margins for anatomic and functional limitations, which are common on specialty sites. There is presently a lack of data of margin positivity after standard excision of vulvar melanomas.

OBJECTIVE

We aim to evaluate the rate of positive margins after standard excision of vulvar melanomas.

MATERIALS AND METHODS

Retrospective cohort study of surgically excised vulvar melanomas from the NCDB diagnosed from 2004 to 2019.

RESULTS

We identified a total of 2,226 cases. Across surgical approaches and tumor stages, 17.2% (Standard Error [SE]: 0.8%) of cases had positive surgical margins. Among tumor stages, T4 tumors were most commonly excised with positive margins (22.9%, SE: 1.5%). On multivariable survival analysis, excision with positive margins was associated with significantly poorer survival (Hazard Ratio 1.299, p = .015).

CONCLUSION

We find that positive margin rates after standard excision of vulvar malignancies are higher than for other specialty site melanomas. Our data suggest that use of surgical approaches with complete margin assessment may improve local control and functional outcomes for patients with vulvar melanoma as they have for patients with other specialty site melanomas.
PhD-Prepared Nurses' Areas of Inquiry
Authors: Roberts Lisa R. , D'Errico Ellen
Published: March 2023

Background:

Nursing science is heavily dependent on nurse scientists with adequate funding. Nurse scientists should be aware of organizations' research agendas and, to the extent possible, align research with stated research priorities. Current information on the demographics of nurse scientists, their projects, and the alignment to known priorities is illusive.

Purpose:

To describe areas of inquiry pursued by PhD-prepared nurses and congruence with the research agendas of nursing organizations.

Methods:

A descriptive, exploratory approach was undertaken with PhD-prepared nurse scientists to gather data about their PhD program, dissertation topic, current work status, productivity, and future recommendations.

Results:

Key findings were that dissertation topics were broad and aligned with research priorities. Elements influencing research productivity are described.

Conclusions:

Understanding current nursing science stewardship and intentionally strategizing for the future of research, academia, and clinical practice will enhance our ability to tailor PhD programs accordingly.
Case Report: Multimodal, Longitudinal Assessment of Retinal Structure and Function following Laser Retinal Injury
Authors: Wang Yiyi , La Tammy T. , Mason Melanie , Tuten William S. , Roorda Austin
Published: March 2023

SIGNIFICANCE

This case report demonstrates the use of novel imaging techniques and functional tests to longitudinally evaluate retinal structure and function after laser retinal injury. The structural and functional prognosis could be predicted with clinical findings, high-resolution retinal imaging, and functional testing.

PURPOSE

We present a laser retinal injury case in which an adaptive optics scanning laser ophthalmoscope and adaptive optics–based psychophysics were used to examine and monitor retinal structure and function after accidental exposure to a 1-W infrared laser beam.

CASE REPORT

A 23-year-old patient was unwittingly exposed to a 1-W, 852-nm continuous-wave laser at work as they noticed a small central blurry spot in the right eye. An initial eye examination was done 1 day after exposure, and the right eye's acuity was 20/25−2. Posterior segment evaluation revealed disrupted outer retina near the right eye's fovea. Adaptive optics imaging 2 weeks after the exposure revealed a 0.50 × 0.75° elliptical area with irregular borders and abnormal cone reflectivity just below the fovea. Starting at 1-month follow-up, structural recovery was observed on optical coherence tomography (OCT). Subsequent adaptive optics imaging showed significant recovery of cone reflectivity. Importantly, adaptive optics microperimetry showed measurable detection thresholds at all affected retinal locations at 6 months. By 10 months, all sites exhibited normal sensitivities.

CONCLUSIONS

Retinal structure and function from laser injury can be visualized and measured with OCT, adaptive optics imaging, and psychophysics. An intact Bruch's membrane on OCT and measurable retinal sensitivity by adaptive optics microperimetry may serve as good biomarkers for retinal recovery.
Eliminating Breast Surgery for Invasive Cancer with Exceptional Response to Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint
Authors: Johnson Helen M , Valero Vicente , Yang Wei T , Smith Benjamin D , Krishnamurthy Savitri , Shen Yu , Lin Heather , Lucci Anthony , Rauch Gaiane M , Kuerer Henry M
Published: March 2023

Background:

Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapies. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence prior to trial expansion.

Study Design:

Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or HER2-positive (HER2+BC) cancer with <2cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in-situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence (IBTR) at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

Results:

Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51-75) and most patients were white (69.2%), non-Hispanic/Latino (84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+B). Mean tumor size was 2.4 centimeters (range 0.9-5.0 cm) before NST and 0.7cm (range 0-1.8cm) post-NST. Seven patients (53.8%) had residual disease identified on VACB; the remaining six (46.2%) comprised the feasibility cohort. At a median follow-up of 44.3 (range 41.3-51.3) months, there were no IBTR in this cohort.

Conclusions:

These early data suggest that omission of breast surgery in patients with invasive TNBC and HER2+BC with no evidence of residual disease on standardized VACB following NST is potentially feasible. Results from the expansion phase of this clinical trial will be reported per protocol pre-specified analyses.
Spatial structure and benefits to hosts allow plasmids with and without post-segregational killing systems to coexist
Authors: Verweij Wilco , Griswold Cortland K.
Published: March 2023

To persist, a plasmid relies on being passed on to a daughter cell, but this does not always occur. Plasmids with post-segregational killing (PSK) systems kill a daughter cell if the plasmid has not been passed on. By killing the host, it also kills competing plasmids in the same host, something competing plasmids without a similar system cannot do. Accordingly, plasmids with PSK systems can displace other plasmids. In nature, plasmids with and without PSK systems coexist and prior theory has suggested this is expected to be very rare or unstable, such that one or the other type of plasmid eventually takes over. Here, we show that if there is spatial structure and plasmids confer benefits to hosts, coexistence of plasmids occurs broadly. Often plasmids confer benefits (even ones with a PSK system) and bacteria are often spatially structured. So, our results may be generally applicable.
Anne Laura Dorinthea McLaren DBE. 26 April 1927—7 July 2007
Authors: Clarke Ann , Johnson FRS Martin H.
Published: March 2023

Anne M
c
Laren DBE was born into a privileged family, which affected her future in two distinct ways. Her cut-glass accent and social confidence were advantageous reminders of this early privilege, but her unrelenting rejection of it was evident in her left-wing egalitarian political and social views and actions. Anne was among the pioneers of research into mammalian development—her experiments on embryonic and fetal development in mice led indirectly to ‘test tube’ babies and contributed to our understanding of the relative roles of soma and germ cells in generating the two sexes. However, it is not only her science for which she will be remembered; her social, educational, ethical and political activities in the cause of science were paramount. She was an articulate, logical and extraordinarily confident speaker, always unrelentingly focused and thoroughly prepared. These qualities made her a formidable member of the Warnock Committee of enquiry, which generated the internationally influential guidelines on how human-assisted reproduction should be regulated. She served for 10 years with distinction on the Human Fertilisation and Embryology Authority, the UK regulatory body that resulted from the Warnock enquiry. She was a founder member, and president, of the Association of Women in Science and Engineering. Her interests extended beyond human welfare to that of animals, and she became involved with conservation and biodiversity preservation programmes internationally. She was elected Foreign Secretary of the Royal Society, the first woman to hold this office in its 332 years.
Parameter inference in a computational model of haemodynamics in pulmonary hypertension
Authors: Colunga Amanda L. , Colebank Mitchel J. ,   REU Program, Olufsen Mette S.
Published: March 2023

Pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg, is characterized by increased pulmonary vascular resistance and decreased pulmonary arterial compliance. There are few measurable biomarkers of PH progression, but a conclusive diagnosis of the disease requires invasive right heart catheterization (RHC). Patient-specific cardiovascular systems-level computational models provide a potential non-invasive tool for determining additional indicators of disease severity. Using computational modelling, this study quantifies physiological parameters indicative of disease severity in nine PH patients. The model includes all four heart chambers, the pulmonary and systemic circulations. We consider two sets of calibration data: static (systolic and diastolic values) RHC data and a combination of static and continuous, time-series waveform data. We determine a subset of identifiable parameters for model calibration using sensitivity analyses and multi-start inference and perform posterior uncertainty quantification. Results show that additional waveform data enables accurate calibration of the right atrial reservoir and pump function across the PH cohort. Model outcomes, including stroke work and pulmonary resistance-compliance relations, reflect typical right heart dynamics in PH phenotypes. Lastly, we show that estimated parameters agree with previous, non-modelling studies, supporting this type of analysis in translational PH research.
Wireless-controlled cubic neural stimulator for free-moving animals
Authors: Liu Xinyu , Su Zhenling , Gao Qingran , Ping Yanna , Xie Hang , Yang Yang , Wang Dongyun
Published: March 2023

An electrical stimulator transmitting information into selected neural circuits is a promising approach for neural prostheses or animal robots. However, traditional stimulators are based on rigid printed circuit board (PCB) technology; technological limitations hindered the development of stimulators, especially for experiments involving free-moving subjects. Here we described a small (1.6 × 1.8 × 1.6 cm), lightweight (4 g, including a 100 mA h lithium battery) and multi-channel (eight unipolar or four bipolar biphasic channels) cubic wireless electrical stimulator exploiting flexible PCB technology. In comparison with the traditional stimulator, an appliance of both flexible PCB and cube structure makes it smaller and lighter, and enhances its stability. Stimulation sequences can be constructed with 100 selectable current levels, 40 selectable frequency levels and 20 selectable pulse-width-ratio levels. Moreover, the distance of wireless communication can reach approximately 150 m. Both
in vitro
and
in vivo
results have demonstrated functionality of the stimulator. The feasibility of remote pigeon's navigation using the proposed stimulator was successfully verified.
‘Quantum supremacy’ revisited: low-complexity, deterministic solutions of the original Deutsch–Jozsa problem in classical physical systems
Authors: Kish Laszlo Bela
Published: March 2023

The
original
Deutsch–Jozsa (oDJ) problem is for an oracle (realized here as a database) of size
N
, where, according to their claim, the deterministic solution of the problem on a classical Turing computer requires O(
N
) computational complexity. They produced the famous Deutsch–Jozsa quantum algorithm that offered an exponential speed-up over the classical computer, namely O[log(
N
)] complexity for the solution in a quantum computer. In this paper, the problem is implemented on an instantaneous noise-based logic processor. It is shown that, similarly to the quantum algorithm, the oDJ problem can deterministically be solved with O[log(
N
)] complexity. The implication is that by adding a truly random coin to a classical Turing machine and using this classical-physical algorithm can also speed up the deterministic solution of the Deutsch–Jozsa problem exponentially, similarly to the quantum algorithm. Then it is realized that the same database and the solution of the Deutsch–Jozsa problem can also be realized by using an identical algorithmic structure in a simpler way, even without noise/random coin. The only lost function in this new system, as compared with noise-based logic, is the ability to do generic parallel logic operations over the whole database. As the latter feature is not needed for the oDJ problem, it is concluded that the problem can be solved on a classical computer with O[log(
N
)] complexity even without a random coin. Therefore, while the oDJ algorithm is a historically important step in the developments of quantum computers, it is insufficient to prove quantum supremacy. Note, there is also a
simplified
Deutsch–Jozsa problem proposed later, which is more popular in the field; however, it is irrelevant for the present paper.
Wave-induced motion of rigid bodies: beads, boats and buildings
Authors: Martin P. A.
Published: March 2023

The determination of rigid-body motion caused by incident waves is a familiar problem in mechanics. Good examples are the motion of a ship in the presence of water waves and the motion of a rigid structure in the presence of seismic waves. The basic goals are to determine the motion of the rigid body and the effects of the motion on the wave field, assuming linear theory is adequate. Although the underlying mathematical problems are similar, several solution methods have evolved, depending on the physical problems of interest. For ship motions, the standard approach is to decompose the problem into seven subproblems, one for each of the six rigid-body modes and one to take account of the incident wave. This approach is reviewed and then adapted to problems in acoustics and to problems in elastodynamics, such as those that arise in simple examples of soil–structure interaction. It is argued that the resulting approach for elastodynamic problems has clear advantages over those currently in use.
Impact of temperature on a ferroelectric interfaced negative capacitance double gate junctionless accumulation mode field effect transistor-compact model
Authors: Yadav Snehlata , Rewari Sonam , Pandey Rajeshwari
Published: March 2023

Ferroelectric interfaced negative capacitance field effect transistors are gaining popularity for low power applications; however, as temperature is a constant influencing factor, further study is required to comprehend how these devices are influenced. Through a proposed compact model, this paper analytically investigates the influence of temperature on a ferroelectric interfaced negative capacitance double gate junctionless accumulation mode field effect transistor. This device integrates the benefits of negative capacitance with the junctionless accumulation mode structure. An extensive comparison of the proposed device is made with the existing structure to evaluate the benefits offered by the ferroelectric layer at different temperatures. The Landau–Khalatnikov equation and Pao–Sah integral are employed to obtain the surface potential and drain current model with temperature variation. Various key parameters of the device have been analysed extensively by varying the temperature from 200 to 500 K. It has been found that internal voltage amplification declines as temperature rises, but the sub-threshold swing increases from 46 to 72 mV decade
−1
with an increase in temperature. Additionally, with a progressive rise in temperature, the loss of gain and degradation of gate capacitance are observed.
A discrete shear lag model of the mechanics of hitchhiker plants, and its prospective application to tendon-to-bone repair
Authors: Hoppe Ethan D. , Birman Victor , Kurtaliaj Iden , Guilliams C. Matt , Pickard Barbara G. , Thomopoulos Stavros , Genin Guy M.
Published: March 2023

Tendon-to-bone repairs often fail when sutures pull through tendon, like a wire through cheese. Repair strength is maximized when loads are balanced equally among all sutures, relative to the pullout resistance of the tendon and the strength of the sutures. This problem of balancing loads across multiple, discrete attachment sites has been solved in nature by hitchhiker plants that proliferate by adhering relatively stiff fruit to relatively soft fur and fabrics through arrays of hooks. We, therefore, studied the fruits of such a plant,
Harpagonella palmeri
, and developed a discrete shear lag analysis of the force distributions in
H. palmeri
's linear arrays of long, slender hooks of varied lengths and spacing. Results suggested that strategies were used by the plant to distribute loads, including variations in the spacing and stiffnesses of hooks that serve to equalize forces over attachment sites. When applying these models to suturing schemes for surgical reattachment of tendon to bone, results suggested that strategies exhibited by
H. palmeri
show promise for balancing forces over sutures, potentially doubling repair strength relative to what could be achieved with a uniform suture distribution. Results suggest a potential pathway for strengthening surgical repairs, and more broadly for optimizing fasteners for bi-material attachment.
Computational investigation of the effect of reduced dynein velocity and reduced cargo diffusivity on slow axonal transport
Authors: Kuznetsov Ivan A. , Kuznetsov Andrey V.
Published: March 2023

Contributions of three components of slow axonal transport (SAT) were studied using a computational model: the anterograde motor (kinesin)-driven component, the retrograde motor (dynein)-driven component and the diffusion-driven component. The contribution of these three components of SAT was investigated in three different segments of the axon: the proximal portion, the central portion, and the distal portion of the axon. MAP1B protein was used as a model system to study SAT because there are published experimental data reporting MAP1B distribution along the axon length and average velocity of MAP1B transport in the axon. This allows the optimization approach to be used to find values of model kinetic constants that give the best fit with published experimental data. The effects of decreasing the value of cargo diffusivity on the diffusion-driven component of SAT and decreasing the value of dynein velocity on the retrograde motor-driven component of SAT were investigated. We found that for the case when protein diffusivity and dynein velocity are very small, it is possible to obtain an analytical solution to model equations. We found that, in this case, the protein concentration in the axon is uniform. This shows that anterograde motor-driven transport alone cannot simulate a variation of cargo concentration in the axon. Most proteins are non-uniformly distributed in axons. They may exhibit, for example, an increased concentration closer to the synapse. The need to reproduce a non-uniform distribution of protein concentration may explain why SAT is bidirectional (in addition to an anterograde component, it also contains a retrograde component).
The effect of sociality on competitive interactions among birds
Authors: Berberi Ilias , Miller Eliot T. , Dakin Roslyn
Published: March 2023

Sociality can provide many benefits, including increased foraging success, reproductive opportunities and defence against predation. How does sociality influence the dominance hierarchies of ecological competitors? Here, we address this question using a large citizen science dataset of competitive interactions among birds foraging at backyard feeders, representing a network of over 55 000 interactions among 68 common species. We first show that species differ in average group size (the number of conspecifics observed together) as a fundamental measure of sociality. When analysing heterospecific competition, we find that sociality is inversely related to dominance. On average, a single individual from a solitary species is more likely to displace a size-matched opponent than a single individual from a social species. Yet, we find that social species gain an increase in their competitive advantage when in the presence of their conspecifics, which may occur as a result of dynamics within their groups. Finally, we show that more social species have relatively fewer dominance interactions with heterospecifics, and more with conspecifics. Overall, these results demonstrate that sociality can influence competition in ecological networks. More social species have decreased competitive ability as individuals, but they may gain competitive ability in groups.
Evolution is driven by natural autoencoding: reframing species, interaction codes, cooperation and sexual reproduction
Authors: Cohen Irun R. , Marron Assaf
Published: March 2023

The continuity of life and its evolution, we proposed, emerge from an interactive group process manifested in networks of interaction. We term this process
survival of the fitted
. Here, we reason that survival of the fitted results from a natural computational process we term
natural autoencoding
. Natural autoencoding works by retaining repeating biological interactions while non-repeatable interactions disappear. (i) We define a species by its
species interaction code
, which consists of a compact description of the repeating interactions of species organisms with their external and internal environments. Species interaction codes are descriptions recorded in the biological infrastructure that enables repeating interactions. Encoding and decoding are interwoven. (ii) Evolution proceeds by natural autoencoding of sustained changes in species interaction codes. DNA is only one element in natural autoencoding. (iii) Natural autoencoding accounts for the paradox of genome randomization in sexual reproduction—recombined genomes are analogous to the diversified inputs required for artificial autoencoding. The increase in entropy generated by genome randomization compensates for the decrease in entropy generated by organized life. (iv) Natural autoencoding and artificial autoencoding algorithms manifest defined similarities and differences. Recognition of the importance of fittedness could well serve the future of a humanly livable biosphere.
Motor recalibration of visual and saccadic maps
Authors: Tyralla Sandra , Pomè Antonella , Zimmermann Eckart
Published: March 2023

How does the brain maintain an accurate visual representation of external space? Movement errors following saccade execution provide sufficient information to recalibrate motor and visual space. Here, we asked whether spatial information for vision and saccades is processed in shared or in separate resources. We used saccade adaptation to modify both, saccade amplitudes and visual mislocalization. After saccade adaptation was induced, we compared participants' saccadic and perceptual localization before and after we inserted ‘no error’ trials. In these trials, we clamped the post-saccadic error online to the predicted endpoints of saccades. In separate experiments, we either annulled the retinal or the prediction error. We also varied the number of ‘no error’ trials across conditions. In all conditions, we found that saccade adaptation remained undisturbed by the insertion of ‘no error’ trials. However, mislocalization decreased as a function of the number of trials in which zero retinal error was displayed. When the prediction error was clamped to zero, no mislocalization was observed at all. The results demonstrate the post-saccadic error is used separately to recalibrate visual and saccadic space.
Transcriptomic responses of sponge holobionts to in situ, seasonal anoxia and hypoxia
Authors: Strehlow Brian W. , Schuster Astrid , Francis Warren R. , Eckford-Soper Lisa , Kraft Beate , McAllen Rob , Nielsen Ronni , Mandrup Susanne , Canfield Donald E.
Published: March 2023

Deoxygenation can be fatal for many marine animals; however, some sponge species are tolerant of hypoxia and anoxia. Indeed, two sponge species,Euryponsp. 2 andHymeraphia stellifera,survive seasonal anoxia for months at a time. To understand their tolerance mechanisms, we performed differential gene expression analyses on the sponges, their mitochondria and their microbial symbionts under in situ conditions of normoxia, hypoxia and anoxia. Each species possessed a unique microbiome, but the microbiomes of each species were dominated by a species-specificThaumarchaeonand aGammaproteobacterium. Holobiont gene expression was species-and oxygen-level dependent, though there were some shared interspecific responses to deoxygenation. In general, few changes occurred in the expression of sponge metabolic genes as a function of oxygenation level, indicating that they may remain metabolically active under anoxia. However, ATP synthesis genes were significantly upregulated under hypoxia when compared to normoxia, and genes for DNA replication were downregulated. Mitochondrial gene expression was effectively unchanged under both hypoxia and anoxia. Nevertheless, both anoxia and hypoxia caused upregulation of heat shock proteins (HSPs), indicating cellular level adaptations to deoxygenation stress. A meta-analysis demonstrated that sponge transcriptional responses to anoxia were distinct from those displayed by other invertebrates while dormant, and the hypothesis of sponge dormancy under anoxia was not supported.Thaumarchaeotasymbionts also upregulated stress response genes in hypoxia, while maintaining expression of oxygen-dependent metabolic pathways under hypoxia and anoxia.Gammaproteobacteriasymbionts showed relatively few noteworthy changes in gene expression in response to anoxia but decreased metabolic gene expression in hypoxia. There was no clear evidence of upregulated anaerobic respiration in the transcriptomes of the sponge holobionts under anoxia or hypoxia. The tolerance of some sponges to prolonged anoxia warrants further investigation and could give them an advantage in future oceans following climate change as well as in ancient oceans when oxygen concentrations were lower than at present.
Hypercholesterolemia aggravates in-stent restenosis in rabbits: a mitigating effect of stent surface modification with CD47-derived peptide
Authors: Fishbein Ilia , Inamdar Vaishali V , Alferiev Ivan S , Bratinov George , Zviman Menekhem M. , Yekhilevsky Anna , Nagaswami Chandrasekaran , Gardiner Kristin L. , Levy Robert J , Stachelek Stanley J
Published: March 2023

Background

Hypercholesterolemia (HC) has previously been shown to augment restenotic response in several animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our present studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model.

Methods and Results

PepCD47 was immobilized on metal foil coupons and stents using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. The relative abundance of the surface-associated cells on bare metal (BM) and pepCD47 foils exposed to whole rabbit blood showed a 40% inhibition of cell attachment on pepCD47-modified surfaces. Likewise, cytokine expression analyzed in buffy coat-derived cells cultured over the BM and pepCD47-derivatized foils demonstrated a M2/M1 increase with pepCD47 coating. Hypercholesterolemic and normocholesterolemic rabbit cohorts underwent bilateral implantation of BM and pepCD47 stents in the iliac location. Hypercholesterolemia increased neointimal growth in comparison with normocholesterolemic animals at 4 weeks post-stenting. These untoward outcomes were mitigated in the arteries of hypercholesterolemic rabbits treated with pepCD47-derivatized stents. Compared to NC animals, inflammatory cytokine immunopositivity and macrophage infiltration of peri-strut areas increased in HC group animals, and was attenuated in the arteries of hypercholesterolemic rabbits treated with pepCD47 stents.

Conclusions

Augmented inflammatory responses triggered by HC underlie severe ISR morphology in hypercholesterolemic rabbits. Blockage of initial platelet and leukocyte attachment to stent struts through CD47 functionalization of stents mitigates pro-restenotic effects of HC.
TALE-based C-to-T base editor for multiple homologous genes with flexible precision
Authors: Hosoda Ayako , Nakazato Issei , Takanashi Hideki , Tsutsumi Nobuhiro , Arimura Shin-ichi
Published: March 2023

Recently a cytidine deaminase-based method for highly efficient C-to-T targeted base editing was developed and has been used with CRISPR-mediated systems. It is a powerful method for genome engineering, although it is prone to off-target effects and has limited targeting scope. Transcription activator-like effector (TALE) -based tools which allow longer recognition sequences than do CRISPR/Cas9 systems, can also be used for targeted C-to-T base editing. Here, we describe a method that efficiently achieved targeted C-to-T substitutions inArabidopsisnuclear genes using cytidine deaminase fused to a TALE DNA-binding domain (TALECD). We used a single pair of TALEs with a novel TALE-repeat unit that can recognize all four DNA bases, especially to allow for variations in the third base of codons in homologous genes. This targeting strategy makes it possible to simultaneously base edit almost identical sites in multiple isoforms of a gene while suppressing off-target substitutions.
Tracking the intensity of the mechanism to produce antigenic diversity by subtelomeric ectopic recombination across the phylogeny ofPlasmodiumparasites
Authors: Martínez Carolina , Cárdenas Heiber , Cerón-Romero Mario A.
Published: March 2023

1

The generation of antigenic diversity, key for parasite virulence, has been investigated in the genusPlasmodium, mainly inPlasmodium falciparum. Cytogenetic and molecular studies have revealed that its subtelomeres are rich in antigenic gene families and undergo ectopic recombination. As a result, these families are highly variable and even species-specific. More recent analyses focused on the phylogenetic mapping ofP. falciparumchromosomes with the bioinformatic tool PhyloChromoMap, showed that ectopic recombination of subtelomeres extends to all chromosomes. Although antigenic gene families have been described in subtelomeres of otherPlasmodiumspecies, the intensity of this mechanism in these species is still unclear. In this study, we investigated to what extent ectopic recombination of subtelomeres drives the generation of antigenic diversity in 19Plasmodiumspecies. To achieve this, we analyzed the profile of gene conservation in maps of all their chromosomes with PhyloChromoMap. Our results suggest that ectopic recombination of subtelomeres is more critical for the diversification ofpirorrif/stevorgenes than other antigenic gene families. Furthermore, its intensity varies among subgenera and was likely acquired and lost multiple times in the phylogeny ofPlasmodium.
The influence of Sex on microRNA expression in Human Skeletal Muscle
Authors: Hiam Danielle , Landen Shanie , Jacques Macsue , Voisin Sarah , Lamon Séverine , Eynon Nir
Published: March 2023

Introduction

Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the top tissues that underpin sex-based differences, yet there is limited research into whether there are sex differences in miRNA expression in skeletal muscle. Further, there is limited literature investigating potential differences between males and females in skeletal muscle miRNA expression following exercise, a well-known modulator of miRNA expression. Therefore, the aim of this study was to investigate the effect of sex on miRNA expression in skeletal muscle at baseline and after an acute bout of exercise.

Methods

MiRNAs were measured using Taqman®miRNA arrays in skeletal muscle of 42 healthy participants from the GeneSMART study (24 males and 20 females aged 18-45 yrs). Differentially expressed miRNAs were identified using mixed linear models adjusted for age. Experimentally validated miRNA gene targets enriched in skeletal muscle were identified in-silico. Over representation analysis was conducted to identify enriched pathways. TransmiR V.2 was used to identify transcription factor (TF)-miR regulatory networks using CHIP-derived data. We further profiled the effects of two sex-biased miRNAs overexpressed in human primary muscle cells lines derived from male and female donors to understand the transcriptome targeted by these miRNAs and investigate and potential sex-specific effects.

Results

A total of 80 miRNAs were differentially expressed in skeletal muscle between the sexes, with 61 miRNAs responding differently to the exercise between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of the muscle cells and numerous metabolic pathways, suggesting that miRNAs are playing a role in programming sex differences in skeletal muscle. Over-expression of sex-biased miRNAs miRNA-30a and miRNA-30c resulted in profound changes to gene expression profiles that were partly specific to the sex of the cell donor in human primary skeletal muscle cells.

Conclusion

We found sex-differences in the expression profile of skeletal muscle miRNAs at baseline and in response to exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism, suggesting that miRNAs play a profound but highly complex role in programming sex-differences in the skeletal muscle phenotype.
Identification of efflux substrates using a riboswitch-based reporter inPseudomonas aeruginosa
Authors: Urdaneta-Páez Verónica , Hamchand Randy , Anthony Karen , Crawford Jason , Sutherland Alan G. , Kazmierczak Barbara I.
Published: March 2023

Pseudomonas aeruginosais intrinsically resistant to many classes of antibiotics, reflecting the restrictive nature of its outer membrane and the action of its numerous efflux systems. However, the dynamics of compound uptake, retention and efflux in this bacterium remain incompletely understood. Here, we exploited the sensor capabilities of a Z-nucleotide sensing riboswitch to create an experimental system able to identify physicochemical and structural properties of compounds that permeate the bacterial cell, avoid efflux, and perturb the folate cycle orde novopurine synthesis. In a first step, a collection of structurally diverse compounds enriched in antifolate drugs was screened for ZTP riboswitch reporter activity in efflux-deficientP. aeruginosa, allowing us to identify compounds that entered the cell and disrupted the folate pathway. These initial hits were then rescreened using isogenic efflux-proficient bacteria, allowing us to separate efflux substrates from efflux avoiders. We confirmed this categorization by measuring intracellular levels of select compounds in the efflux-deficient and - proficient strain using high resolution LC-MS. This simple yet powerful method, optimized for high throughput screening, enables the discovery of numerous permeable compounds that avoid efflux and paves the way for further refinement of the physicochemical and structural rules governing efflux in this multi-drug resistant Gram-negative pathogen.

Importance

Treatment ofPseudomonas aeruginosainfections has become increasingly challenging. The development of novel antibiotics against this multi-drug resistant bacterium is a priority, but many drug candidates never achieve effective concentrations in the bacterial cell due due to its highly restrictive outer membrane and the action of multiple efflux pumps. Here, we develop a robust and simple reporter system inP. aeruginosato screen chemical libraries and identify compounds that either enter the cell and remain inside, or enter the cell and are exported by efflux systems. This approach enables developing rules of compound uptake and retention inP. aeruginosathat will lead to more rational design of novel antibiotics.